Affinage

SYNE1

Nesprin-1 · UniProt Q8NF91

Length
8797 aa
Mass
1011.1 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SYNE1/Nesprin-1 is a large multi-isoform scaffold protein that mechanically couples the nucleus to the cytoskeleton and anchors nuclei and organelles in muscle and other tissues (PMID:10878022, PMID:19864491). Its C-terminal KASH domain inserts into the outer nuclear membrane and binds SUN2 to form the LINC complex, linking the nucleoskeleton (emerin, lamin A/C) across the nuclear envelope to the cytoskeleton; its N-terminal alpha-actinin-type actin-binding domain binds and bundles F-actin (PMID:15093733, PMID:17761684, PMID:19008300). Through these connections nesprin-1 positions and anchors myonuclei, clusters synaptic nuclei at the neuromuscular junction, and transmits mechanical strain to the nucleus, functions established by KASH-domain and isoform knockout mice that show defective nuclear positioning, impaired strain transmission, and respiratory failure (PMID:17267447, PMID:19864491). Nesprin-1 also serves as the predominant nuclear anchor for the microtubule cytoskeleton, recruiting centrosomal protein PCM-1, which in turn assembles dynein-dynactin and kinesin motor complexes to align nuclei along microtubules, and its KASH-dependent microtubule anchoring drives the force transmission underlying Lmna-linked cardiac pathology (PMID:27802164, PMID:35925868). Loss of the outer nuclear membrane LINC complex impairs biomechanical gene regulation and chromatin positioning in cardiomyocytes (PMID:24586179), and SYNE1/nesprin-1 disruption causes Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and recessive arthrogryposis through impaired nesprin/emerin/lamin/SUN2 interactions (PMID:17761684, PMID:19542096, PMID:28398466). Beyond nuclear-cytoskeletal coupling, distinct nesprin-1 isoforms localize to the Golgi and mediate retrograde Golgi-to-ER trafficking, participate in cytokinesis via the kinesin II subunit KIF3B, and—in the case of a cytoplasmic p50 isoform—tether processing-body mRNP complexes to microtubules to support miRNA-mediated silencing (PMID:12808039, PMID:14709720, PMID:15276322, PMID:24862572).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 Medium

    Establishing that SYNE1 encodes a nuclear envelope protein of striated and smooth muscle with spectrin repeats and a KASH domain defined it as a candidate nucleoskeleton-cytoskeleton linker and revealed selective enrichment at synaptic myonuclei.

    Evidence Protein domain analysis and immunofluorescence with denervation/regeneration in mice

    PMID:10878022

    Open questions at the time
    • Molecular binding partners at the nuclear envelope not yet identified
    • Functional consequence of synaptic enrichment unknown
  2. 2004 High

    Demonstrating that the N-terminal actin-binding domain binds and bundles F-actin established the cytoskeletal end of the linkage, while a spectrin-repeat fragment binding KIF3B placed nesprin-1 in kinesin-II-mediated cytokinesis.

    Evidence In vitro F-actin binding/bundling assays, immunofluorescence, yeast two-hybrid and co-precipitation with dominant-negative phenotypes

    PMID:14709720 PMID:15093733

    Open questions at the time
    • Whether actin binding and KIF3B binding occur in the same isoform unclear
    • Cytokinesis role rests on dominant-negative fragments rather than full-length depletion
  3. 2004 Medium

    Identification of Golgi-binding domains and dominant-negative blockade of retrograde PDI recycling extended nesprin-1 function to membrane trafficking distinct from nuclear coupling.

    Evidence Epitope-tagged fragment expression, dominant-negative overexpression, immunofluorescence of Golgi/ER cargo and COP-I markers

    PMID:12808039 PMID:15276322

    Open questions at the time
    • Which endogenous isoform mediates Golgi function not defined
    • Direct trafficking machinery partners not identified
  4. 2007 High

    Defining the nesprin-1/emerin/lamin A/C network and showing EDMD mutations impair these bindings and mislocalize emerin/SUN2 connected nesprin-1 to a Mendelian muscular dystrophy mechanism.

    Evidence Mutation screening, reciprocal co-immunoprecipitation, siRNA knockdown phenocopy, immunofluorescence

    PMID:17761684

    Open questions at the time
    • Quantitative contribution of each interaction to nuclear integrity unresolved
    • Structural basis of complex assembly not determined
  5. 2007 High

    KASH-domain deletion in mice abolishing synaptic nuclear clustering, disrupting innervation, and—with Syne-2—causing neonatal respiratory failure established myonuclear anchorage as an essential in vivo function requiring SUN2 interaction.

    Evidence Single and double KASH-domain knockout mice, histology, motor nerve anatomy, co-IP of nesprin-1 with SUN2

    PMID:17267447 PMID:19008300

    Open questions at the time
    • Redundancy mechanisms between Syne-1 and Syne-2 not fully mapped
    • Link between nuclear clustering and synaptic function incompletely defined
  6. 2009 High

    Complete and KASH-domain isoform knockouts showed nesprin-1 is required for nuclear positioning, anchorage, and strain transmission in muscle, while human splice-site mutations causing KASH loss established it as a cause of recessive arthrogryposis and dilated cardiomyopathy.

    Evidence Isoform-specific knockout mice with nuclear mechanics readouts; linkage analysis and patient mutation detection with mouse phenotyping; lamin A/C binding of nesprin-1α isoform

    PMID:19542096 PMID:19864491 PMID:19944109

    Open questions at the time
    • Genotype-phenotype basis for distinct clinical outcomes unclear
    • Tissue-specific isoform contributions not dissected
  7. 2010 Medium

    Nesprin-1 knockdown abolishing strain-induced cell reorientation and altering focal adhesions/traction demonstrated that nuclear-cytoskeletal coupling balances actomyosin tension and mechanotransduction.

    Evidence siRNA knockdown in endothelial cells, cyclic strain assay, traction force microscopy

    PMID:20655839

    Open questions at the time
    • Downstream signaling linking nesprin-1 to adhesion remodeling not defined here
    • Isoform responsible not specified
  8. 2012 Medium

    Co-IP showing nesprin-1 interacts with multiple actin isoforms in cardiomyocytes broadened the actin connectivity underlying nuclear anchorage.

    Evidence Co-immunoprecipitation and Western blotting in Lmna-knockout cardiomyocytes

    PMID:21156181

    Open questions at the time
    • Direct versus indirect actin associations not distinguished
    • Functional relevance of each isoform interaction unresolved
  9. 2014 High

    Diverse isoforms localizing to stress fibers, microtubules, nucleolus, and nuclear matrix, plus cardiac double knockouts impairing biomechanical gene regulation and chromatin positioning, established nesprin-1 as a versatile scaffold upstream of mechanically driven transcription.

    Evidence RACE/EST isoform cloning with tagged-isoform localization; cardiac-specific Syne-1/Syne-2 double knockout with chromatin and gene-expression profiling

    PMID:22768332 PMID:24586179

    Open questions at the time
    • Mechanism linking LINC disruption to specific transcriptional changes not detailed
    • Roles of individual isoforms in vivo not separated
  10. 2014 Medium

    Discovery that a cytoplasmic p50 isoform tethers processing-body mRNPs to microtubules and that nesprin-1 binds MSH2/MSH6 and influences DNA damage markers revealed RNA-silencing and genome-maintenance roles distinct from nuclear anchorage.

    Evidence Isoform expression with dominant-negative, co-IP of Ago2/Rck/p54/GW182 and MSH2/MSH6, miRNA silencing reporters, DNA damage marker analysis; RNAi with angiogenesis/migration assays

    PMID:24781983 PMID:24862572 PMID:24931616

    Open questions at the time
    • MSH2/MSH6 interaction is a single-lab Co-IP without reciprocal structural validation
    • Physiological significance of PB and DDR roles in tissues not established
  11. 2014 Medium

    The Drosophila ortholog Msp-300 controlling NMJ glutamate receptor subunit composition extended nesprin function to synaptic receptor regulation.

    Evidence KASH-domain deletion and tissue-specific RNAi in Drosophila, NMJ electrophysiology, receptor immunostaining, locomotion rescue

    PMID:24492984

    Open questions at the time
    • Conservation of this synaptic role in mammals not shown
    • Molecular pathway linking nesprin to receptor composition unknown
  12. 2016 Medium

    Showing nesprin-1 recruits PCM-1 and thereby dynein-dynactin and kinesin to align myotube nuclei, and that a muscle-specific α2 isoform is switched on during myogenesis, mechanistically connected nuclear positioning to microtubule motor recruitment and differentiation.

    Evidence siRNA knockdown in differentiating C2C12 with immunofluorescence epistasis; qPCR and isoform-specific antibody imaging across myogenic stages; Matr3 identified by Co-IP/MS as a PB-associated partner

    PMID:27350129 PMID:27733621 PMID:27802164

    Open questions at the time
    • Direct nesprin-1/PCM-1 binding interface not defined
    • How isoform switching is regulated transcriptionally unclear
  13. 2017 High

    Mapping C-terminal disease variants that disrupt lamin A/C, SUN2, and kinesin light chain (KLC) binding via a LEWD motif, augment ERK signaling, and impair differentiation linked specific molecular interactions to dilated cardiomyopathy and to ROCK/FHOD1-dependent stiffness adaptation defects.

    Evidence GST pull-down and Co-IP of nesprin-1/lamin/SUN2 and nesprin-1/KLC interactions, ERK analysis, C2C12 differentiation, zebrafish cardiac assay; traction force microscopy with ROCK inhibition and FHOD1 depletion in patient cells

    PMID:28398466 PMID:28455503

    Open questions at the time
    • Relative contributions of ERK versus structural disruption to disease unclear
    • FHOD1/ROCK axis tested mainly in patient-derived cells in vitro
  14. 2019 Medium

    Characterizing CPG2, a brain-specific protein encoded within the SYNE1 locus that regulates glutamate receptor internalization and is reduced in bipolar disorder brains, established a separate neuronal output of the locus relevant to psychiatric disease.

    Evidence Postmortem protein quantification, promoter reporter assays, missense SNP functional characterization

    PMID:30610203

    Open questions at the time
    • Relationship between CPG2 and full-length nesprin-1 isoforms not resolved
    • Causality versus association with bipolar disorder not established
  15. 2021 Medium

    Systematic domain dissection of the C. elegans ortholog ANC-1 showed the spectrin-like region plus transmembrane span—not the KASH or actin-binding domains alone—is essential for anchoring nuclei, ER, mitochondria, and lipid droplets, reframing nesprin function as broad organelle anchorage from the ER membrane.

    Evidence Domain-deletion genetics and live-cell organelle imaging in C. elegans

    PMID:33860766

    Open questions at the time
    • Generality of ER-anchoring model to mammalian nesprin-1 not confirmed
    • Molecular basis of multi-organelle anchoring undefined
  16. 2023 High

    CRISPR KASH disruption in cardiomyocytes showed nesprin-1 LINC complexes are the predominant nuclear anchor for microtubule cytoskeleton and motor components, and that removing this anchor suppresses Lmna-linked cardiac pathology by reducing microtubule-mediated nuclear force.

    Evidence CRISPR KASH-domain disruption, immunofluorescence of microtubule components, genetic epistasis with Lmna mutation

    PMID:35925868

    Open questions at the time
    • Mechanism by which microtubule force damages Lmna-mutant nuclei not fully resolved
    • Therapeutic generalizability beyond the model unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct nesprin-1 isoforms are deployed across tissues to selectively execute nuclear anchorage, microtubule/actin coupling, organelle positioning, mRNP/RNA-silencing, and trafficking functions—and how specific interaction losses map onto the spectrum of muscular, cardiac, neurological, and psychiatric phenotypes—remains unresolved.
  • No integrated structural model of the full-length scaffold and its multivalent interactions
  • Isoform-specific in vivo functions not separated
  • Causal links between molecular interaction defects and each disease phenotype incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 3 GO:0003723 RNA binding 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005635 nuclear envelope 4 GO:0005856 cytoskeleton 4 GO:0005794 Golgi apparatus 2 GO:0005730 nucleolus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-397014 Muscle contraction 4 R-HSA-9609507 Protein localization 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-8953854 Metabolism of RNA 2
Partners
EMDKIF3BKLC1LMNAMSH2MSH6PCM1SUN2
Complex memberships
LINC complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Syne-1 (SYNE1) encodes a protein associated with nuclear envelopes in skeletal, cardiac, and smooth muscle cells, containing multiple spectrin repeats similar to dystrophin/utrophin and a domain homologous to Klarsicht (KASH domain). In adult skeletal muscle, Syne-1 is selectively enriched at synaptic nuclei beneath the postsynaptic membrane at the neuromuscular junction, becoming concentrated postnatally and remaining enriched after denervation or degeneration/regeneration. Protein domain analysis, immunofluorescence microscopy, denervation/regeneration experiments in mice The Journal of biological chemistry Medium 10878022
2003 Syne-1 localizes to the Golgi complex in addition to the nuclear envelope. Two distinct Golgi-binding domains were identified in the central portion of the protein by expression of epitope-tagged fragments. Expression of one Golgi-binding domain as a dominant-negative inhibitor caused the Golgi to collapse into a condensed juxtanuclear structure. Expression of epitope-tagged fragments in MDBK and COS cells, immunofluorescence microscopy, dominant-negative overexpression Molecular biology of the cell Medium 12808039
2004 The N-terminal alpha-actinin-type actin-binding domain (ABD) of Enaptin/Nesprin-1 binds F-actin in vivo and in vitro and causes actin bundle formation. Antibodies against the ABD localize the protein at F-actin-rich structures, focal contacts, and the nuclear envelope. In vitro F-actin binding assay, in vivo localization by immunofluorescence, actin bundling assay Experimental cell research High 15093733
2004 A spectrin-repeat fragment of Syne-1 associates with the C-terminal tail domain of the kinesin II subunit KIF3B, as shown by yeast two-hybrid and co-precipitation. Both Syne-1 and KIF3B localize to the central spindle and midbody during cytokinesis in a detergent-resistant, ATP-sensitive manner. Dominant-negative expression of the Syne-1 fragment or KIF3B tail domain causes accumulation of binucleate cells, implicating Syne-1 in cytokinesis via kinesin II-mediated membrane vesicle transport to the spindle midbody. Yeast two-hybrid, co-precipitation, dominant-negative overexpression, immunofluorescence localization during cytokinesis Journal of cell science Medium 14709720
2004 Expression of dominant-negative Syne-1 fragments blocks retrograde recycling of the ER-resident protein PDI (protein disulfide isomerase), which accumulates in the Golgi. These fragments also alter the distribution of the KDEL receptor and COP-I coat protein beta-COP, implicating Syne-1 in retrograde vesicular trafficking from the Golgi to the ER. Dominant-negative fragment expression, immunofluorescence of PDI/KDEL receptor/beta-COP, Golgi morphology analysis Biochimica et biophysica acta Medium 15276322
2007 Nesprin-1 and nesprin-2 bind emerin and lamins A/C and form a network linking the nucleoskeleton to the inner and outer nuclear membranes, sarcomere, and actin cytoskeleton. Missense mutations in SYNE1/SYNE2 associated with EDMD cause impaired nesprin/emerin/lamin binding interactions and mislocalization of emerin and SUN2. siRNA knockdown of nesprin-1 in normal fibroblasts reproduces nuclear morphology defects and emerin/SUN2 mislocalization. Mutation screening, co-immunoprecipitation of nesprin/emerin/lamin complexes, siRNA knockdown, immunofluorescence of emerin and SUN2 Human molecular genetics High 17761684
2007 Deletion of the KASH domain of Syne-1 in mice abolishes synaptic nuclear clustering at the neuromuscular junction and disrupts non-synaptic nuclear organization in skeletal muscle. Loss of synaptic nuclei significantly disrupts innervation sites and causes longer motor nerve branches. Syne-1;Syne-2 double-knockout mice die of respiratory failure at birth, demonstrating cooperative roles in myonuclear anchorage essential for respiration. Conditional KASH-domain knockout mice (single and double), histology, motor nerve anatomy Development (Cambridge, England) High 17267447
2008 Deletion of the C-terminal KASH domain of nesprin-1 produces an EDMD-like phenotype in mice (hindlimb weakness, kyphoscoliosis, muscle pathology, cardiac conduction defects). The mutant nesprin-1 no longer co-immunoprecipitates with SUN2, demonstrating that the KASH domain is required for nesprin-1/SUN2 interaction within the LINC complex. C-terminus knockout mouse model, co-immunoprecipitation of nesprin-1 and SUN2, cardiac electrophysiology, histopathology Human molecular genetics High 19008300
2009 Nesprin-1 is essential for normal nuclear positioning and anchorage in skeletal muscle in vivo. Knockout mice lacking all C-terminal spectrin-repeat isoforms exhibit defective nuclear positioning and anchorage, and nuclei in muscle fibers lacking nesprin-1 show ineffective strain transmission. Complete nesprin-1 isoform knockout mouse, nuclear positioning analysis, nuclear deformation/strain transmission testing Human molecular genetics High 19864491
2009 A splice-site mutation in SYNE-1 causing loss of the C-terminal KASH domain results in autosomal recessive arthrogryposis. The mutation produces premature stop codons and absence of the transmembrane KASH domain, and mice lacking the KASH domain display a similar myopathic phenotype. Linkage analysis, mutation detection, mRNA analysis, mouse KASH-domain knockout phenotyping Human molecular genetics Medium 19542096
2009 The nesprin-1α isoform binds lamin A/C. An R374H missense variant in nesprin-1α is associated with dilated cardiomyopathy; KASH-domain-deleted mice develop cardiomyopathy with cardiac conduction system disease and elongated cardiomyocyte nuclei with reduced heterochromatin. Patient variant identification, KASH-domain knockout mouse model, cardiac electrophysiology, echocardiography, nuclear morphology analysis Journal of molecular and cellular cardiology Medium 19944109
2010 siRNA knockdown of nesprin-1 in endothelial cells abolishes cyclic strain-induced cell reorientation, increases nuclear height, increases focal adhesions and substrate traction, and decreases migration speed. These results are consistent with the nucleus balancing actomyosin tension through nesprin-1 connections. siRNA knockdown, cyclic strain assay, confocal microscopy, traction force microscopy, focal adhesion quantification Biophysical journal Medium 20655839
2011 Nesprin-1 functionally interacts with multiple actin isoforms (nuclear G-actin, cytoskeletal γ-actin, α-cardiac actin, α-smooth muscle actin) in cardiomyocytes, as demonstrated by immunoprecipitation and Western blotting in Lmna-knockout mice. Co-immunoprecipitation, Western blotting in Lmna−/− cardiomyocytes Journal of molecular and cellular cardiology Medium 21156181
2012 Nesprin-1 isoforms containing alternative start/termination sites localize to actin stress fibers, focal adhesions, microtubules, the nucleolus, nuclear matrix, and nuclear envelope in a cell-type-dependent manner, demonstrating that nesprin-1 acts as a versatile intracellular scaffold beyond nuclear-cytoskeletal coupling. RACE analysis, EST database screening, PCR validation, expression of epitope-tagged isoforms, immunofluorescence localization in fibroblasts and U2OS cells PloS one Medium 22768332
2014 Ablation of both nesprin-1 and nesprin-2 in cardiomyocytes (but neither alone) causes early-onset cardiomyopathy with altered nuclear positioning, shape, and chromatin positioning, and impairs gene expression changes in response to biomechanical stimuli, placing the outer nuclear membrane LINC complex upstream of biomechanical gene regulation. Cardiac-specific double knockout mice, echocardiography, nuclear morphology analysis, chromatin positioning, biomechanical gene expression profiling PLoS genetics High 24586179
2014 A 50-kDa nesprin-1 isoform (p50Nesp1) localizes to processing bodies (PBs) where it acts as a microtubule-associated protein linking mRNP complexes to microtubules. Overexpression of dominant-negative p50Nesp1 displaces Rck/p54 from microtubules, reduces PB movement and cross-talk with stress granules, impairs miRNA-mediated silencing, and causes cell death. p50Nesp1 interacts with Ago2 and Rck/p54 in an RNA-dependent manner and with GW182 in a microtubule-dependent manner. Isoform cloning and expression, dominant-negative overexpression, immunoprecipitation, live-cell imaging, miRNA silencing reporter assay The Journal of cell biology High 24862572
2014 Nesprin-1 depletion in endothelial cells increases spread area and stress fiber assembly, reduces migration into a cell-free area, and decreases angiogenic loop formation in vitro. Emerin localization to the nuclear envelope is reduced upon nesprin-1 or nesprin-2 depletion. RNAi knockdown, wound healing/scratch assay, in vitro angiogenesis assay, immunofluorescence Cytoskeleton (Hoboken, N.J.) Medium 24931616
2014 Nesprin-1 knockdown by RNAi reduces MSH2 and MSH6 levels, alters Chk1/Chk2 phosphorylation, reduces Ku70 and impairs its recruitment to DNA after hydroxyurea treatment, and increases γH2AX foci without exogenous DNA damage, identifying MSH2 and MSH6 as nesprin-1 binding partners and placing nesprin-1 in the DNA damage response pathway. RNAi knockdown, co-immunoprecipitation (MSH2/MSH6 as interactors), Western blotting of DNA damage markers, immunofluorescence of γH2AX and Ku70 Nucleus (Austin, Tex.) Medium 24781983
2014 Drosophila Nesprin-1 ortholog Msp-300 controls glutamate receptor subunit composition at the neuromuscular junction; loss of its KASH domain decreases the proportion of GluRIIA-containing receptors at the NMJ, causing locomotion defects that are rescued by GluRIIA overexpression. Drosophila KASH-domain deletion, tissue-specific RNAi, electrophysiology at NMJ, immunostaining of glutamate receptor subunits, locomotion rescue assay Cellular and molecular life sciences : CMLS Medium 24492984
2016 Nuclear alignment in myotubes requires nesprin-1 to recruit centrosome protein PCM-1 to the nuclear envelope at the onset of differentiation. PCM-1 in turn recruits dynein-dynactin and kinesin motor complexes, positioning nuclei along microtubules in myotubes. siRNA knockdown in differentiating C2C12 myoblasts, immunofluorescence of PCM-1, dynein/dynactin, and kinesin at the nuclear envelope Journal of cell science Medium 27802164
2016 The short muscle-specific isoform nesprin-1-α2 is undetectable in pre-differentiation myoblasts but appears at the nuclear rim in post-mitotic multinucleate myotubes, reaching highest levels in fetal muscle, indicating its expression is switched on during myogenesis alongside other differentiation markers. Quantitative PCR, monoclonal antibody development, immunofluorescence in myoblasts/myotubes/fetal/regenerating muscle BMC cell biology Medium 27350129
2016 Identification of novel nesprin-1 binding partners by co-immunoprecipitation combined with mass spectrometry revealed matrin-3 (Matr3) as a nesprin-1 interactor. Matr3 localizes to mRNA processing bodies (PBs), is part of PB mRNP complexes, and regulates miRNA-mediated gene silencing. Co-immunoprecipitation with mass spectrometry, immunofluorescence, miRNA silencing reporter assay Molecular biology of the cell Medium 27733621
2017 Three novel SYNE1 variants (R8272Q, S8381C, N8406K) at the C-terminus disrupt nesprin-1 interactions with lamin A/C and SUN2 (shown by GST pull-down) and augment ERK pathway activation. During C2C12 differentiation, nesprin-1 interacts with kinesin light chains KLC-1/2 via a LEWD domain in its C-terminus (shown by co-immunoprecipitation and GST pull-down); DCM-associated mutants disrupt this interaction and impair myoblast differentiation and fusion. GST pull-down (nesprin-1/lamin/SUN2 and nesprin-1/KLC interactions), co-immunoprecipitation, ERK pathway analysis, C2C12 differentiation assay, zebrafish cardiac development assay Human molecular genetics High 28398466
2017 Pathogenic mutations in LMNA or SYNE-1 reduce the ability of human muscle cell precursors to adapt to substrates of different stiffness, causing contractile stress fiber accumulation, increased focal adhesions, and higher traction force. These defects are mediated by ROCK-dependent regulation of the formin FHOD1; depletion or inactivation of FHOD1 rescues morphology in mutant cells. Traction force microscopy, ROCK inhibition, FHOD1 depletion/inactivation, immunofluorescence of actin structures in patient-derived cells Scientific reports Medium 28455503
2019 CPG2, a brain-specific protein encoded within the SYNE1 locus, localizes to excitatory postsynaptic sites and regulates glutamate receptor internalization. CPG2 protein levels are significantly decreased in postmortem brain tissue from bipolar disorder patients. Genetic variants in the CPG2 promoter region negatively affect gene expression, and missense SNPs in CPG2 coding regions affect CPG2 expression, localization, and synaptic function. Postmortem brain protein quantification, promoter reporter assay, missense SNP functional characterization (expression/localization/synaptic function assays) Molecular psychiatry Medium 30610203
2020 Activity-dependent accumulation of Msp300/Nesprin-1 in the postsynaptic compartment of the Drosophila larval NMJ is regulated by the RNA-binding protein Syncrip/hnRNP Q. Syncrip binds msp300 transcripts in vivo, and msp300 mRNA forms ribosome-rich granules containing eIF4E at the synapse. Elevated neural activity alters the dynamics of Syp and the number of msp300:Syp:eIF4E granules, indicating translational regulation. Single-molecule RNA imaging, co-IP of Syp with msp300 transcripts, live-cell imaging of RNP granule dynamics, genetic knockdown of Syp The Journal of cell biology Medium 32040548
2021 C. elegans ANC-1 (Nesprin-1/2 ortholog) positions nuclei, ER, mitochondria, and lipid droplets. Neither the KASH domain nor the calponin homology (CH/actin-binding) domain alone is essential; deletions in the spectrin-like region cause significant defects, and only combined disruption of the spectrin region plus the transmembrane span recapitulates the null phenotype. ANC-1 localizes to the ER membrane and extends into the cytoplasm to anchor multiple organelles. Domain deletion genetics in C. elegans, live-cell organelle imaging, nuclear positioning quantification eLife Medium 33860766
2023 Nesprin-1 LINC complexes (via its KASH domain) serve as the predominant nuclear envelope anchor for microtubule cytoskeleton components, including nucleation activities and motor complexes, in mouse cardiomyocytes. CRISPR disruption of the nesprin-1 KASH domain removes microtubule cytoskeleton proteins from the nucleus. Disrupting the KASH domain suppresses Lmna-linked cardiac pathology, likely by reducing microtubule-mediated nuclear force transmission. CRISPR KASH-domain disruption in mouse cardiomyocytes, immunofluorescence of microtubule components at nucleus, genetic epistasis with Lmna mutation Human molecular genetics High 35925868

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Human molecular genetics 419 17761684
2019 SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes. Cell death discovery 328 31231549
2006 Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Nature genetics 262 17159980
2000 Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction. The Journal of biological chemistry 231 10878022
2007 Syne-1 and Syne-2 play crucial roles in myonuclear anchorage and motor neuron innervation. Development (Cambridge, England) 227 17267447
1996 The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse. Genes & development 198 8682296
2004 Enaptin, a giant actin-binding protein, is an element of the nuclear membrane and the actin cytoskeleton. Experimental cell research 164 15093733
2008 Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy-like phenotype in mice. Human molecular genetics 160 19008300
2010 Actomyosin tension exerted on the nucleus through nesprin-1 connections influences endothelial cell adhesion, migration, and cyclic strain-induced reorientation. Biophysical journal 152 20655839
2009 Nesprin 1 is critical for nuclear positioning and anchorage. Human molecular genetics 125 19864491
2009 Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis. Human molecular genetics 122 19542096
2014 Targeted ablation of nesprin 1 and nesprin 2 from murine myocardium results in cardiomyopathy, altered nuclear morphology and inhibition of the biomechanical gene response. PLoS genetics 118 24586179
2009 Nesprin-1 mutations in human and murine cardiomyopathy. Journal of molecular and cellular cardiology 113 19944109
2008 Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function. American journal of human genetics 110 18514160
2012 Multiple novel nesprin-1 and nesprin-2 variants act as versatile tissue-specific intracellular scaffolds. PloS one 101 22768332
2005 Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia. Biological psychiatry 100 16229822
2016 SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large multi-centre study. Brain : a journal of neurology 99 27086870
2006 Ric-8B promotes functional expression of odorant receptors. Proceedings of the National Academy of Sciences of the United States of America 89 16754875
2004 A role for the spectrin superfamily member Syne-1 and kinesin II in cytokinesis. Journal of cell science 88 14709720
2017 Novel nesprin-1 mutations associated with dilated cardiomyopathy cause nuclear envelope disruption and defects in myogenesis. Human molecular genetics 82 28398466
2010 The high-affinity cAMP-specific phosphodiesterase 8B controls steroidogenesis in the mouse adrenal gland. Molecular pharmacology 79 21187369
2010 ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 78 20056644
2008 The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor. Hepatology (Baltimore, Md.) 78 18668687
2012 Association at SYNE1 in both bipolar disorder and recurrent major depression. Molecular psychiatry 76 22565781
2017 Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3. Virology 75 29294448
2012 cAMP-specific phosphodiesterases 8A and 8B, essential regulators of Leydig cell steroidogenesis. Molecular pharmacology 70 22232524
2016 Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1. Journal of cell science 64 27802164
2018 Complete genome sequence and the expression pattern of plasmids of the model ethanologen Zymomonas mobilis ZM4 and its xylose-utilizing derivatives 8b and 2032. Biotechnology for biofuels 63 29743953
2003 Golgi localization of Syne-1. Molecular biology of the cell 61 12808039
2001 Enhanced invasion and tumor growth of fibroblast growth factor 8b-overexpressing MCF-7 human breast cancer cells. Cancer research 60 11358849
2014 Nesprin-1 and nesprin-2 regulate endothelial cell shape and migration. Cytoskeleton (Hoboken, N.J.) 59 24931616
2012 Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26. PloS one 59 22693595
2011 Ric-8B is a GTP-dependent G protein alphas guanine nucleotide exchange factor. The Journal of biological chemistry 58 21467038
2001 FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells. Oncogene 54 11420691
2020 Bone morphogenetic protein 8B promotes the progression of non-alcoholic steatohepatitis. Nature metabolism 50 32694734
2013 SYNE1 mutations in autosomal recessive cerebellar ataxia. JAMA neurology 49 23959263
2008 Ric-8B interacts with G alpha olf and G gamma 13 and co-localizes with G alpha olf, G beta 1 and G gamma 13 in the cilia of olfactory sensory neurons. Molecular and cellular neurosciences 49 18462949
2002 Heparin/Heparan sulfate domains in binding and signaling of fibroblast growth factor 8b. The Journal of biological chemistry 49 12077148
2015 Estrogens increase expression of bone morphogenetic protein 8b in brown adipose tissue of mice. Biology of sex differences 46 25866617
2010 Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination. The Journal of biological chemistry 44 20133939
1988 Dissection of 5' upstream sequences for selective expression of the Nicotiana plumbaginifolia rbcS-8B gene. Molecular & general genetics : MGG 43 3226423
2016 Homozygous SYNE1 mutation causes congenital onset of muscular weakness with distal arthrogryposis: a genotype-phenotype correlation. European journal of human genetics : EJHG 42 27782104
2017 Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1. Scientific reports 41 28455503
2006 The human severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein is distinct from its counterpart in animal SARS-CoV and down-regulates the expression of the envelope protein in infected cells. Virology 39 16876844
2021 Liver X Receptor Alpha Activation Inhibits Autophagy and Lipophagy in Hepatocytes by Dysregulating Autophagy-Related 4B Cysteine Peptidase and Rab-8B, Reducing Mitochondrial Fuel Oxidation. Hepatology (Baltimore, Md.) 38 32557804
2016 Epidemiological and pathological investigation of fowl aviadenovirus serotypes 8b and 11 isolated from chickens with inclusion body hepatitis in Spain (2011-2013). Avian pathology : journal of the W.V.P.A 38 27928940
2002 Genomic organization, chromosomal localization, and alternative splicing of the human phosphodiesterase 8B gene. Biochemical and biophysical research communications 38 12372422
2007 Diminished phosphodiesterase-8B potentiates biphasic insulin response to glucose. Endocrinology 37 17991719
2017 Immunogenicity and protective efficacy of virus-like particles and recombinant fiber proteins in broiler-breeder vaccination against fowl adenovirus (FAdV)-8b. Vaccine 36 28396209
2021 The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning in C. elegans independently from its KASH or actin-binding domains. eLife 33 33860766
2019 Kinesin-8B controls basal body function and flagellum formation and is key to malaria transmission. Life science alliance 33 31409625
2010 Autosomal-dominant striatal degeneration is caused by a mutation in the phosphodiesterase 8B gene. American journal of human genetics 33 20085714
1998 Cloning, molecular characterization, and expression of an endo-polygalacturonase-encoding gene from Saccharomyces cerevisiae IM1-8b. FEMS microbiology letters 33 9682473
2014 FOXE1 and SYNE1 genes hypermethylation panel as promising biomarker in colitis-associated colorectal neoplasia. Inflammatory bowel diseases 32 24280874
2014 Nesprin-1 role in DNA damage response. Nucleus (Austin, Tex.) 32 24781983
2024 Leveraging GPT-4 for identifying cancer phenotypes in electronic health records: a performance comparison between GPT-4, GPT-3.5-turbo, Flan-T5, Llama-3-8B, and spaCy's rule-based and machine learning-based methods. JAMIA open 30 38962662
2018 Uncovering the potential of CD44v/SYNE1/miR34a axis in salivary fluids of oral cancer patients. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 30 29315816
2014 Drosophila Nesprin-1 controls glutamate receptor density at neuromuscular junctions. Cellular and molecular life sciences : CMLS 30 24492984
2011 SUMO E3 ligases are expressed in the retina and regulate SUMOylation of the metabotropic glutamate receptor 8b. The Biochemical journal 30 21288202
2023 Nesprin-1 LINC complexes recruit microtubule cytoskeleton proteins and drive pathology in Lmna-mutant striated muscle. Human molecular genetics 29 35925868
2019 First report of fowl aviadenovirus serotypes FAdV-8b and FAdV-11 associated with inclusion body hepatitis in commercial broiler and broiler-breeder flocks in Turkey. Archives of virology 29 31676996
2010 Nesprin-1 and actin contribute to nuclear and cytoskeletal defects in lamin A/C-deficient cardiomyopathy. Journal of molecular and cellular cardiology 29 21156181
2020 SYNE1 mutation may enhance the response to immune checkpoint blockade therapy in clear cell renal cell carcinoma patients. Aging 28 33031058
2016 Specific localization of nesprin-1-α2, the short isoform of nesprin-1 with a KASH domain, in developing, fetal and regenerating muscle, using a new monoclonal antibody. BMC cell biology 27 27350129
2009 FGF-8b induces growth and rich vascularization in an orthotopic PC-3 model of prostate cancer. Journal of cellular biochemistry 26 19415685
2009 Phosphodiesterase 8B gene polymorphism is associated with subclinical hypothyroidism in pregnancy. The Journal of clinical endocrinology and metabolism 25 19820008
2019 SP1-SYNE1-AS1-miR-525-5p feedback loop regulates Ang-II-induced cardiac hypertrophy. Journal of cellular physiology 24 30652310
2018 SYNE1-ataxia: Novel genotypic and phenotypic findings. Parkinsonism & related disorders 24 30573412
2016 Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations. Journal of neurology 24 27178001
2014 Mammalian microtubule P-body dynamics are mediated by nesprin-1. The Journal of cell biology 24 24862572
2019 Nesprin-1 impact on tumorigenic cell phenotypes. Molecular biology reports 23 31741263
2016 Autosomal Recessive Cerebellar Ataxia type 1 mimicking multiple sclerosis: A report of two siblings with a novel mutation in SYNE1 gene in a Saudi family. Journal of the neurological sciences 22 28017257
2011 Increased expression of Syne1/nesprin-1 facilitates nuclear envelope structure changes in embryonic stem cell differentiation. Developmental dynamics : an official publication of the American Association of Anatomists 22 21932307
2006 Expression and functional characterization of the putative protein 8b of the severe acute respiratory syndrome-associated coronavirus. FEBS letters 22 16753150
2019 Bone Morphogenetic Protein-8B Expression is Induced in Steatotic Hepatocytes and Promotes Hepatic Steatosis and Inflammation In Vitro. Cells 21 31096638
2014 Nesprin-1 has key roles in the process of mesenchymal stem cell differentiation into cardiomyocyte-like cells in vivo and in vitro. Molecular medicine reports 21 25339194
2020 Syncrip/hnRNP Q is required for activity-induced Msp300/Nesprin-1 expression and new synapse formation. The Journal of cell biology 20 32040548
2019 Elevated expression of cellular SYNE1, MMP10, and GTPase1 and their regulatory role in hepatocellular carcinoma progression. Protoplasma 20 31428857
2010 ATPase Class I Type 8B Member 1 and protein kinase C zeta induce the expression of the canalicular bile salt export pump in human hepatocytes. Pediatric research 20 19809379
2004 The spectrin family member Syne-1 functions in retrograde transport from Golgi to ER. Biochimica et biophysica acta 19 15276322
2021 Molecular characterization of Malaysian fowl adenovirus (FAdV) serotype 8b species E and pathogenicity of the virus in specific-pathogen-free chicken. Journal of veterinary science 18 34313038
2021 Epidemiological and molecular analysis of circulating fowl adenoviruses and emerging of serotypes 1, 3, and 8b in Egypt. Heliyon 18 34977398
2018 Identifying SYNE1 Ataxia With Novel Mutations in a Chinese Population. Frontiers in neurology 18 30619065
2007 Auditory-motor and cognitive aspects in area 8B of macaque monkey's frontal cortex: a premotor ear-eye field (PEEF). Experimental brain research 18 18038127
2021 Expression and clinical significance of SYNE1 and MAGI2 gene promoter methylation in gastric cancer. Medicine 17 33530176
2020 Juvenile amyotrophic lateral sclerosis with complex phenotypes associated with novel SYNE1 mutations. Amyotrophic lateral sclerosis & frontotemporal degeneration 17 32870032
2017 A novel SYNE1 gene mutation in a Chinese family of Emery-Dreifuss muscular dystrophy-like. BMC medical genetics 17 28583108
2020 Fowl Adenoviruses Type 8b Isolated from Chickens with Inclusion Body Hepatitis in Japan. Avian diseases 16 33205180
2019 Genetic variants in the bipolar disorder risk locus SYNE1 that affect CPG2 expression and protein function. Molecular psychiatry 16 30610203
2023 Structures of Ric-8B in complex with Gα protein folding clients reveal isoform specificity mechanisms. Structure (London, England : 1993) 15 36931277
2023 Nesprin-1: novel regulator of striated muscle nuclear positioning and mechanotransduction. Biochemical Society transactions 15 37171063
2020 Transcriptomic Profiles of Zymomonas mobilis 8b to Furfural Acute and Long-Term Stress in Both Glucose and Xylose Conditions. Frontiers in microbiology 15 32038596
2020 Down-Regulation of Lnc-CYP7A1-1 Rejuvenates Aged Human Mesenchymal Stem Cells to Improve Their Efficacy for Heart Repair Through SYNE1. Frontiers in cell and developmental biology 15 33330489
2019 Boosting Ethanol Productivity of Zymomonas mobilis 8b in Enzymatic Hydrolysate of Dilute Acid and Ammonia Pretreated Corn Stover Through Medium Optimization, High Cell Density Fermentation and Cell Recycling. Frontiers in microbiology 15 31636624
2011 The Ric-8B gene is highly expressed in proliferating preosteoblastic cells and downregulated during osteoblast differentiation in a SWI/SNF- and C/EBPbeta-mediated manner. Molecular and cellular biology 15 21606199
2021 Young and early-onset dilated cardiomyopathy with malignant ventricular arrhythmia and sudden cardiac death induced by the heterozygous LDB3, MYH6, and SYNE1 missense mutations. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 13 33949037
2016 Identification of novel nesprin-1 binding partners and cytoplasmic matrin-3 in processing bodies. Molecular biology of the cell 13 27733621
2012 Fibroblast growth factor 8b causes progressive stromal and epithelial changes in the epididymis and degeneration of the seminiferous epithelium in the testis of transgenic mice. Biology of reproduction 13 22423049
2010 Haplotype analysis of the promoter region of phosphodiesterase type 8B (PDE8B) in correlation with inactivating PDE8B mutation and the serum thyroid-stimulating hormone levels. Thyroid : official journal of the American Thyroid Association 13 20373981
2023 SYNE1 Mutation Is Associated with Increased Tumor Mutation Burden and Immune Cell Infiltration in Ovarian Cancer. International journal of molecular sciences 12 37762518

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