Affinage

GPSM2

G-protein-signaling modulator 2 · UniProt P81274

Length
684 aa
Mass
76.7 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPSM2 (LGN) is a multivalent scaffolding protein that functions as an autoinhibited conformational switch to orient the mitotic spindle and establish cell polarity in diverse tissues. In its closed state, intramolecular binding between the N-terminal TPR domain and C-terminal GoLoco motifs prevents partner engagement; Gαi-GDP binding to the GoLoco motifs (which act as guanine nucleotide dissociation inhibitors) releases autoinhibition, enabling the TPR domain to recruit NuMA to the cell cortex, forming a Gαi/LGN/NuMA ternary complex that captures astral microtubules via dynein to orient the spindle (PMID:15537540, PMID:23665171, PMID:15946753). Cortical LGN is spatially restricted by aPKC phosphorylation at Ser401 and 14-3-3 binding (excluding it from the apical domain), by Ric-8A-catalyzed Gαi-GTP release (which dissociates the complex), and by competitive interactions with mInscuteable, E-cadherin, Afadin, and Dlg1 that regulate its recruitment in epithelial, neural, and endothelial contexts (PMID:20933426, PMID:16275912, PMID:21816348, PMID:26751642, PMID:28045117). Beyond mitotic spindle orientation, GPSM2 forms a Gαi3-dependent nanodomain at stereocilia tips that drives elongation and row 1 identity in auditory hair cells, and loss-of-function mutations in GPSM2 cause Chudley-McCullough syndrome (sensorineural deafness with brain malformations) and nonsyndromic deafness DFNB82 (PMID:28387217, PMID:30827920, PMID:22578326, PMID:20602914).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    The identification of LGN as a direct Gαi2-binding protein with TPR-like repeats and GoLoco motifs established the molecular architecture that would later explain its scaffolding function.

    Evidence Yeast two-hybrid screen and in vitro binding assay with recombinant proteins

    PMID:8973305

    Open questions at the time
    • No cellular function assigned
    • Binding specificity across Gα family unknown
    • No structural information
  2. 2002 High

    Discovery that LGN directly binds NuMA's C-terminal tail and blocks NuMA-microtubule interaction revealed LGN as a regulator of microtubule organization, providing the first link to the mitotic apparatus.

    Evidence In vitro microtubule stabilization assays, frog egg extracts, domain mapping

    PMID:12445386

    Open questions at the time
    • Whether LGN-NuMA interaction occurs in vivo during mitosis unclear
    • LGN cortical targeting mechanism unknown
  3. 2003 Medium

    Demonstration that LGN cortical localization requires Gα subunits and the GoLoco domain established the paradigm of Gαi-dependent cortical targeting, linking heterotrimeric G-protein signaling to spindle orientation.

    Evidence Overexpression of truncated domains, co-expression of Gα subunits, cell cycle analysis in mammalian cells

    PMID:12925752

    Open questions at the time
    • Relied on overexpression; endogenous loss-of-function not tested
    • Mechanism by which Gαi anchors LGN at cortex unresolved
  4. 2004 High

    The FRET-based demonstration that LGN is an autoinhibited conformational switch — opened by Gαi or NuMA to allow simultaneous binding of both partners — provided the mechanistic basis for ternary complex assembly at the cortex.

    Evidence FRET biosensor, Co-IP, live cell imaging of spindle oscillations

    PMID:15537540

    Open questions at the time
    • Structural basis of autoinhibition not yet atomic-resolution
    • Regulation of the switch in vivo unknown
  5. 2005 High

    Biochemical characterization of all four GoLoco motifs as GDIs selective for Gαi over Gαo, together with demonstration that Ric-8A catalytically dissociates Gαi-GDP/LGN/NuMA complexes, defined the nucleotide cycle that controls LGN complex assembly and disassembly.

    Evidence Surface plasmon resonance, GDI assays with individual motifs; in vitro reconstitution with purified Ric-8A, LGN, NuMA, Gαi

    PMID:15946753 PMID:16275912

    Open questions at the time
    • Ric-8A regulation in vivo during mitosis not demonstrated
    • Stoichiometry of Gαi binding to LGN in cells unknown
  6. 2007 High

    Genetic loss-of-function in chick and mouse neuroepithelia showed that LGN is required for planar spindle orientation in neural progenitors, and that misorientation causes premature differentiation, establishing the physiological consequence of LGN disruption in vivo.

    Evidence Dominant-negative/overexpression in chick spinal cord; conditional knockout mouse neuroepithelium with division plane analysis

    PMID:17934458 PMID:18084280

    Open questions at the time
    • Whether spindle misorientation directly causes fate change or is permissive unclear
    • Upstream polarity cues directing LGN localization in neuroepithelium not identified
  7. 2010 High

    Multiple converging studies established how LGN is spatially restricted: aPKC phosphorylation at Ser401 recruits 14-3-3 to exclude LGN from the apical cortex, while Ric-8A/Gαi and the actin cytoskeleton promote lateral cortical localization, explaining how polarity information is translated into spindle orientation.

    Evidence Phosphorylation mapping by MS, S401A mutagenesis in 3D MDCK cysts, siRNA/pertussis toxin in HeLa cells, immunofluorescence

    PMID:20385777 PMID:20479129 PMID:20933426

    Open questions at the time
    • Other kinases regulating LGN not excluded
    • How Gαi is itself asymmetrically distributed not resolved
  8. 2010 Medium

    Human genetic studies linked GPSM2 loss-of-function to nonsyndromic deafness DFNB82 and subsequently Chudley-McCullough syndrome, establishing GPSM2 as essential for inner ear and brain development.

    Evidence Homozygosity mapping and exome sequencing in consanguineous families

    PMID:20602914 PMID:22578326

    Open questions at the time
    • Precise cellular mechanism of hearing loss not defined at this point
    • Brain malformation mechanism inferred but not directly demonstrated
  9. 2011 High

    Crystal structures of LGN-TPR in complex with NuMA and mInscuteable revealed that these partners bind competitively to overlapping surfaces on the TPR concave face, establishing the structural basis for sequential complex formation during asymmetric versus symmetric divisions.

    Evidence Crystal structures (2.6 Å), SPR affinity measurements, structure-based mutagenesis

    PMID:21816348 PMID:22074847 PMID:22171003

    Open questions at the time
    • Temporal regulation of mInsc/NuMA switching in vivo unclear
    • Whether tetramerization occurs in mammalian cells not tested
  10. 2012 High

    Crystal structures of GoLoco motifs GL3/GL4 bound to Gαi-GDP, combined with the autoinhibited LGN structure showing GL34 helices contacting TPR4-7, provided the atomic-resolution explanation for how Gαi-GDP binding releases autoinhibition by competing for the same GoLoco surfaces.

    Evidence Crystal structures of GL3/GL4–Gαi-GDP and autoinhibited LGN, GDI assays

    PMID:22952234 PMID:23665171

    Open questions at the time
    • Full-length LGN structure not available
    • Dynamics of conformational switching in cells not measured at atomic level
  11. 2014 High

    Identification of Dlg1, activated ERMs, and genetic epistasis of Par3-mInsc-Gαi3 expanded the upstream cortical cue network: Dlg1 acts as a cortical anchor for LGN, ERMs link LGN-NuMA to the actin cortex, and mInsc cooperates with Gαi3 to polarize LGN for asymmetric divisions in epidermis.

    Evidence Direct binding/pulldown for Dlg1-LGN; phosphomimetic ERM mutants with in utero electroporation; double-mutant epistasis in mouse epidermis

    PMID:24958772 PMID:25016959 PMID:25202028

    Open questions at the time
    • How these cues are integrated into a unified spatial map is not modeled
    • Relative contributions of Dlg1 vs ERM vs Afadin in different tissues not compared
  12. 2016 High

    Crystal structure of Afadin-LGN and identification of SAPCD2 as a negative regulator expanded the repertoire of LGN cortical anchors and modulators, showing Afadin bridges LGN to F-actin and SAPCD2 competes with NuMA for LGN binding.

    Evidence Crystallography of Afadin-LGN complex, siRNA in Caco-2 cysts and mouse retina; Co-IP and functional studies for SAPCD2

    PMID:26751642 PMID:26766442

    Open questions at the time
    • Whether SAPCD2 and Afadin operate in the same or parallel pathways unclear
    • SAPCD2 mechanism confirmed in limited tissue contexts
  13. 2017 High

    Discovery that LGN binds E-cadherin's cytosolic tail in interphase and is displaced by NuMA at mitotic onset provided a cell-cell junction-based mechanism for coupling adhesion geometry to spindle orientation; a parallel study showed phospho-VE-cadherin recruits LGN at endothelial junctions for flow sensing.

    Evidence Direct binding/competition assays for E-cadherin-LGN-NuMA; Co-IP with phospho-Y658 VE-cadherin, siRNA, in vivo vascular remodeling

    PMID:28045117 PMID:28712573

    Open questions at the time
    • Whether E-cadherin-LGN interaction is universal across epithelia not tested
    • How VE-cadherin-LGN coupling leads to mechanotransduction downstream unclear
  14. 2017 High

    Super-resolution imaging revealed that GPSM2-Gαi3 forms an ~200 nm nanodomain at stereocilia tips, dependent on Myo15a and whirlin, driving actin-based stereocilia elongation — establishing a non-mitotic role for GPSM2 in polarized actin growth.

    Evidence Mouse knockout, single-molecule tracking, super-resolution imaging of hair cells and neuronal growth cones

    PMID:28387217

    Open questions at the time
    • Mechanism by which GPSM2-Gαi3 promotes actin polymerization at tips not defined
    • Whether GDI activity is required at stereocilia tips not tested
  15. 2019 High

    Systematic genetic epistasis placed GPSM2-GNAI downstream of MYO15A-EPS8 at row 1 stereocilia tips, showing GPSM2 stabilizes the tip complex and confers row identity, linking molecular nanodomain composition to hair bundle morphogenesis.

    Evidence Multiple mouse mutant combinations (Gpsm2, Gnai, Myo15a, Whrn), confocal and super-resolution imaging over developmental time

    PMID:30827920

    Open questions at the time
    • Direct biochemical reconstitution of the stereocilia tip complex not achieved
    • How row 1 identity information feeds back to differential elongation rates unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: how the multiple cortical cues (Dlg1, ERMs, Afadin, E-cadherin, mInsc) are spatially and temporally integrated to pattern LGN; the mechanism by which GPSM2-Gαi3 promotes actin polymerization at stereocilia tips; and the full-length structure of LGN in its various partner-bound states.
  • No full-length LGN structure available
  • Mechanism of GPSM2-driven actin elongation at stereocilia tips undefined
  • Integrated quantitative model of cortical cue hierarchy absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 12 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1640170 Cell Cycle 13 R-HSA-1266738 Developmental Biology 6 R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 2
Partners
AFDNCDH1DLG1GNAI1GNAI2GNAI3INSCNUMA1
Complex memberships
Gαi/LGN/NuMA ternary complexPar3/mInsc/LGN complexWHRN-GPSM2-GNAI stereocilia tip complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 LGN (GPSM2) was identified as a novel protein that directly interacts with the alpha-subunit of the heterotrimeric GTP-binding protein Gαi2, confirmed by yeast two-hybrid screening and in vitro binding assays with recombinant proteins. LGN contains 10 Leu-Gly-Asn repeats and mosaic domain structure including N-terminal TPR-like repeats and C-terminal GoLoco motifs. Yeast two-hybrid screen of human B cell cDNA library; in vitro binding assay with recombinant proteins Gene High 8973305
2002 LGN directly binds the C-terminal tail of NuMA and blocks NuMA's ability to bind and stabilize microtubules through steric exclusion, as the MT-binding domain on NuMA overlaps with the LGN-binding domain by ten amino acid residues. In vitro microtubule stabilization assays, frog egg extracts, direct binding assays, domain mapping Current biology : CB High 12445386
2002 LGN localizes to the midbody structure separating daughter cells during the later stages of mitosis in PC12 and COS7 cells, and its subcellular localization is regulated by the cell cycle and external stimuli, suggesting a role in cytokinesis. Immunocytochemistry in primary neuronal cultures and dividing cell lines The Journal of biological chemistry Medium 11832491
2003 LGN cortical localization during mitosis depends on Gα subunits of heterotrimeric G proteins and requires the C-terminal GoLoco domain; cortical localization is also dependent on microfilaments. Interfering with LGN function in cultured cell lines disrupts cell cycle progression. Overexpression of truncated protein domains, co-overexpression of Gα subunits, actin disruption experiments, cell cycle analysis Molecular biology of the cell Medium 12925752
2004 Mammalian LGN (GPSM2) acts as a conformational switch: in its closed state, the N-terminal TPR domain and C-terminal GoLoco domain interact intramolecularly; NuMA or Gαi can disrupt this autoinhibited state, allowing LGN to simultaneously bind both NuMA and Gαi, recruiting them to the cell cortex. This was demonstrated using a FRET biosensor. Overexpression of Gαi or LGN causes pronounced oscillation of metaphase spindles, and NuMA binding to LGN is required for spindle movements. FRET biosensor, Co-IP, overexpression studies, live cell imaging Cell High 15537540
2005 GPSM2/LGN contains four GoLoco motifs that each function as guanine nucleotide dissociation inhibitors (GDIs) for Gαi1, Gαi2, and Gαi3, with high selectivity for Gαi subunits over Gαo. All four GoLoco motifs bind Gαi1 by surface plasmon resonance. Surface plasmon resonance binding assays, fluorescence-based nucleotide-binding GDI assays with individual purified GoLoco motifs Biochimica et biophysica acta High 15946753
2005 Ric-8A dissociates Gαi-GDP/LGN/NuMA complexes catalytically in vitro, releasing activated Gαi-GTP and concomitantly liberating NuMA from LGN, suggesting that Ric-8A-stimulated activation of Gαi regulates microtubule pulling forces during mitosis. In vitro biochemical reconstitution assays with purified mammalian Ric-8A, LGN, NuMA, and Gαi Proceedings of the National Academy of Sciences of the United States of America High 16275912
2005 LGN (GPSM2) is expressed in the inner segments of photoreceptor cells where it colocalizes with transducin α-subunit (Gtalpha) after light-dependent translocation; LGN and Gtalpha coprecipitate from retinal extracts, and the GPR domain of LGN potently inhibits receptor-mediated guanine nucleotide exchange and GTPase activity of transducin. Immunostaining, serial tangential sectioning, immunoblot, co-precipitation, in vitro GTPase and nucleotide exchange assays Molecular and cellular neurosciences Medium 15737739
2006 LGN modulates GIRK (G protein-activated inwardly rectifying potassium) channel activity: LGN increases basal GIRK current but reduces receptor-mediated GIRK activation by Gi/Go-coupled receptors. In hippocampal neurons, LGN hyperpolarizes resting membrane potential via increased basal GIRK activity. LGN RNAi reduces endogenous basal GIRK activity and increases neuronal excitability. Electrophysiology, overexpression, lentiviral RNAi in hippocampal neurons, mammalian cell expression systems Neuron High 16701207
2007 LGN is located at the cell cortex and spindle poles of chick neuroepithelial progenitors and regulates spindle movements and orientation to promote planar divisions; interfering with LGN function randomizes the plane of division, causing daughter cells to exit the neuroepithelium prematurely without affecting cell fate. In vivo overexpression/dominant-negative in chick spinal cord, immunostaining, time-lapse imaging Nature neuroscience High 17934458
2007 LGN (mammalian GPSM2) knockout in mouse neuroepithelium randomizes the orientation of normally planar neuroepithelial divisions, causing loss of apical membrane from daughter cells and converting them into abnormally localized progenitors; planar mitosis ensures neuroepithelial self-renewal by allowing one daughter to inherit both apical and basal compartments. Conditional knockout mouse, immunostaining, analysis of division plane and cell fate Nature cell biology High 18084280
2010 Ric-8A and Gαi recruit LGN, NuMA, and dynein to the cell cortex during mitosis to orient the metaphase spindle of mammalian adherent cells. Pertussis toxin (which blocks Ric-8A binding to Gαi) and reduction of Ric-8A or Gαi expression all impaired cortical LGN and NuMA localization and disturbed integrin-dependent spindle orientation. siRNA knockdown, pertussis toxin treatment, immunofluorescence, live cell imaging of GFP-tubulin HeLa cells Molecular and cellular biology High 20479129
2010 Par3 ensures correct spindle orientation in epithelial cells by activating aPKC, which phosphorylates LGN on Ser401, recruiting 14-3-3 protein and inhibiting LGN binding to Gαi, thereby excluding LGN from the apical cortex. A LGN S401A mutant mislocalizes over the entire cell cortex causing spindle orientation and lumen defects. siRNA silencing, phosphorylation mapping by mass spectrometry, apically tethered aPKC rescue, 14-3-3 co-IP, mutant LGN overexpression in MDCK 3D cysts Current biology : CB High 20933426
2010 LGN localizes to the lateral cell cortex (excluded from the apical cortex) during mitosis of MDCK cells and is required for directing spindle orientation during cystogenesis; disruption of LGN cortical localization, or its interaction with NuMA or Gαi, causes spindle misorientation and abnormal cystogenesis. Apical exclusion of LGN is mediated by aPKC. siRNA knockdown, dominant-negative mutants, artificial membrane mistargeting, 3D MDCK cyst culture, immunofluorescence The Journal of cell biology High 20385777
2010 GPSM2 is localized to apical surfaces of hair cells and supporting cells in the mouse inner ear during embryonic development; a nonsense mutation causing early truncation of GPSM2 causes nonsyndromic hearing loss DFNB82, linking GPSM2's role in cell polarity/spindle orientation to cochlear development. Whole exome sequencing, homozygosity mapping, immunolocalization in mouse inner ear American journal of human genetics Medium 20602914
2010 The serine/threonine kinase PBK/TOPK phosphorylates LGN/GPSM2 at Thr450 during mitosis (G2/M phase); a T450A mutant causes growth suppression and aberrant chromosomal segregation, indicating that this phosphorylation is required for normal LGN function in cell division. Western blot with phospho-specific detection, overexpression of T450A mutant, siRNA knockdown, cell cycle synchronization Genes, chromosomes & cancer Medium 20589935
2011 Crystal structures of LGN TPR domain in complex with NuMA and with mInscuteable (mInsc) reveal that mInsc and NuMA bind competitively to LGN TPR motifs with mInsc binding preferentially; this mutual exclusivity suggests that Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division. Crystal structure determination, in vitro competition/binding assays, cell biology studies Molecular cell High 21816348
2011 Crystal structure of LGN TPR domain complexed with human mInsc-LBD (2.6 Å) reveals three binding modules of mInsc (α-helix, extended region, β-sheet) running antiparallel along the concave TPR superhelix. Structure-based mutagenesis shows mInsc binds LGN with highest affinity (Kd ~2.4 nM), effectively displacing NuMA, Frmpd proteins, and the LGN C-terminus; mInsc-LGN interaction stabilizes LGN and determines intracellular localization of mInsc. Crystal structure (2.6 Å), mutagenesis, surface plasmon resonance, cell biology Proceedings of the National Academy of Sciences of the United States of America High 22074847
2011 LGN and NuMA form a lateral belt at the lateral cell cortex (excluded from apical cortex) in chick neuroepithelial cells during spindle orientation; the LGN/NuMA/Gαi complex is necessary for spindle movements and regulates the dynamics of planar spindle orientation. 3D live imaging of GFP-centrosomes, immunostaining, dominant-negative and siRNA perturbations in chick neuroepithelium The Journal of cell biology High 21444683
2011 Inscuteable (Insc) competes with NuMA for LGN binding in vitro, displaying higher affinity; Insc can open the LGN conformational switch but specifically inhibits the Mud/NuMA pathway while allowing the Dlg pathway to remain active. Crystal structure of Drosophila Pins/Insc complex, in vitro competition assays, cell biology Proceedings of the National Academy of Sciences of the United States of America High 22171003
2012 GPSM2 mutations (two single-base deletions, a nonsense mutation, and a splice-site mutation) cause Chudley-McCullough syndrome characterized by severe sensorineural hearing loss and brain malformations (frontal polymicrogyria, partial agenesis of corpus callosum, gray matter heterotopia), establishing that defects in GPSM2-mediated mitotic spindle orientation underlie both the hearing loss and brain malformations. Homozygosity mapping, whole-exome sequencing in eight families, brain imaging American journal of human genetics Medium 22578326
2012 Crystal structures of LGN GoLoco motifs GL3 and GL4 in complex with Gαi·GDP reveal that a 'double Arg finger' sequence (RΨ(D/E)(D/E)QR) is responsible for LGN GL binding to GDP on Gαi; the C-terminal GL domain of LGN binds four molecules of Gαi·GDP, and GLs are potent guanine nucleotide dissociation inhibitors. Crystal structures of LGN GL3/GL4 with Gαi·GDP, in vitro GDI assays The Journal of biological chemistry High 22952234
2013 Crystal structure of a truncated LGN reveals that two consecutive GoLoco (GL) motifs form a minimal TPR-binding unit; GL34 forms parallel α-helices binding to the concave surface of TPR4-7, preventing LGN from binding other targets. This autoinhibited conformation is mediated by a mode of GL/TPR interaction distinct from GL/Gαi·GDP complexes. Crystal structure of autoinhibited LGN, biochemical binding assays Structure (London, England : 1993) High 23665171
2013 LGN associates with cytoplasmic dynein heavy chain (DYNC1H1) in a Gαi-regulated manner; LGN is required for mitotic cortical localization of DYNC1H1, which in turn modulates cortical LGN accumulation. FRAP analysis shows cortical LGN is dynamic and its turnover depends on astral microtubules and dynein. Actin filaments counteract dynein-mediated LGN transport from cortex to spindle poles. Co-IP, siRNA knockdown, FRAP analysis, live cell imaging Molecular biology of the cell High 23389635
2014 The activated ERM (ezrin/radixin/moesin) proteins, phosphorylated by SLK kinase at mitotic entry, promote the polarized cortical association of LGN and NuMA; impairing ERM activation disrupts LGN-NuMA localization and spindle orientation both in mammalian cells and in mouse embryonic neocortical progenitors in vivo. siRNA knockdown, phosphomimetic/non-phosphorylatable ERM mutants, micropatterned adhesive substrates, in utero electroporation in mouse neocortex The Journal of cell biology High 24958772
2014 Dlg1 directly interacts with LGN and is required for cortical localization of the LGN complex and planar spindle orientation in the chick neuroepithelium; homogeneously localized Dlg1 can recruit LGN to the mitotic cortex in human cells, acting primarily as a cortical anchor upstream of LGN. Pulldown/direct binding assays, siRNA knockdown in human cells, in vivo electroporation in chick neuroepithelium, live imaging The Journal of cell biology High 25202028
2014 Par3-mInsc and Gαi3 act cooperatively to polarize LGN and promote perpendicular (asymmetric) divisions in murine epidermis; loss of each gene alone randomizes division angles, while combined loss of Gnai3 and mInsc causes mostly planar divisions akin to loss of LGN. Conditional genetics and lentiviral in vivo RNAi in mouse epidermis, double-mutant epistasis analysis Nature cell biology High 25016959
2015 The GoLoco motifs of GPSM2/LGN are essential for hearing; mice with targeted deletion of C-terminal GoLoco motifs (LgnΔC) are profoundly deaf, show hair bundle misorientation and stereocilia malformations; Gαi and aPKC are dependent on Lgn for proper localization; Lgn acts as a PCP effector downstream of core PCP proteins, and kinocilium is required for proper Lgn localization. Targeted mouse mutation, auditory testing (ABR), immunofluorescence, epistasis with PCP mutants Mammalian genome High 26662512
2016 Afadin directly and concomitantly binds F-actin and LGN; the crystal structure of human Afadin in complex with LGN shows resemblance to the LGN-NuMA complex interface. In mitosis, Afadin is required for cortical accumulation of LGN and NuMA above spindle poles in an F-actin-dependent manner, serving as a mechanical anchor between dynein and cortical F-actin. Crystallography, direct binding assays, siRNA knockdown in Caco-2 cysts, immunofluorescence Nature structural & molecular biology High 26751642
2016 SAPCD2 is a novel LGN-interacting protein that negatively regulates the cortical localization of LGN, likely by competing with NuMA for LGN binding; loss of SAPCD2 randomizes spindle orientation in epithelial cells and mouse retinal progenitors in vivo, while overexpression disrupts cyst morphogenesis. Co-IP (SAPCD2-LGN interaction), siRNA in epithelial cells, in vivo mouse retinal analysis, 3D cyst culture Developmental cell Medium 26766442
2017 LGN binds directly to the cytosolic tail of E-cadherin and localizes at cell-cell adhesions; on mitotic entry, NuMA is released from the nucleus and competes LGN from E-cadherin to form the LGN/NuMA complex at cell-cell contacts, stabilizing cortical associations of astral microtubules to orient the mitotic spindle. Direct binding assay (E-cadherin tail pulldown), Co-IP, competitive displacement assay, siRNA, live cell imaging Nature communications High 28045117
2017 Phosphorylation of VE-cadherin on Y658 by src family kinases induces dissociation of p120ctn and allows binding of LGN at endothelial junctions; this LGN recruitment is required for multiple flow responses in vitro and in vivo including inflammatory signaling and flow-dependent vascular remodeling. Co-IP, phospho-specific antibodies, siRNA knockdown, in vitro flow assays, in vivo mouse vascular remodeling Current biology : CB High 28712573
2017 GPSM2 (Gpsm2) and its partner Gαi3 are required for actin-rich stereocilia elongation in auditory and vestibular hair cells; Gpsm2 defines an ~200 nm nanodomain at the tips of stereocilia, and its localization there requires Gαi3, myosin 15 (Myo15a), and whirlin. Loss of Gpsm2 decreases outgrowth and disrupts actin dynamics in neuronal growth cones. Mouse knockout, single-molecule tracking, super-resolution imaging, immunofluorescence in hair cells and neurons Nature communications High 28387217
2018 Crystal structure of Drosophila LGN (Pins) in complex with the asymmetric domain of Inscuteable reveals a tetrameric arrangement; Insc:LGN tetramers form stable cores of Par3-Insc-LGN-GαiGDP complexes that cannot be dissociated by NuMA. In mammary stem cells, the Insc-bound pool of LGN acts independently of microtubule motors to promote asymmetric fate specification. Crystal structure, SAXS, biochemical reconstitution, mammary stem cell functional assays Nature communications High 29523789
2019 GPSM2-GNAI defines an exclusive nanodomain at the tips of the tallest (row 1) stereocilia and confers row 1 identity; GPSM2 operates downstream of MYO15A-EPS8 as part of an extended stereocilia tip complex (WHRN-GPSM2-GNAI recruited by MYO15A-EPS8), and stabilizes larger amounts of MYO15A-EPS8 specifically in row 1. In the absence of GPSM2 or GNAI, bundles retain an embryonic-like organization. Comprehensive genetic mouse epistasis (Gpsm2, Gnai, Myo15a, Whrn mutants), immunofluorescence, confocal and super-resolution imaging of hair bundles over time Current biology : CB High 30827920

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Nature 931 15716953
2007 Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis. Nature cell biology 400 18084280
2004 Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 320 15537540
2000 A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Current biology : CB 278 10753746
2005 Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature 271 16357871
2006 The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nature cell biology 267 16648843
2003 Fireworks in the primate retina: in vitro photodynamics reveals diverse LGN-projecting ganglion cell types. Neuron 234 12526769
2006 Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nature cell biology 215 16648846
2005 Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell 214 16377571
2010 Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82. American journal of human genetics 207 20602914
2007 Control of planar divisions by the G-protein regulator LGN maintains progenitors in the chick neuroepithelium. Nature neuroscience 201 17934458
2003 Asymmetrically distributed C. elegans homologs of AGS3/PINS control spindle position in the early embryo. Current biology : CB 198 12814548
2010 Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. Current biology : CB 193 20933426
2010 LGN regulates mitotic spindle orientation during epithelial morphogenesis. The Journal of cell biology 153 20385777
1976 Properties of LGN cells in kittens reared with convergent squint: a neurophysiological demonstration of amblyopia. Experimental brain research 146 1269559
2001 Visual response properties of neurons in the LGN of normally reared and visually deprived macaque monkeys. Journal of neurophysiology 140 11353027
2010 Ric-8A and Gi alpha recruit LGN, NuMA, and dynein to the cell cortex to help orient the mitotic spindle. Molecular and cellular biology 139 20479129
2002 LGN blocks the ability of NuMA to bind and stabilize microtubules. A mechanism for mitotic spindle assembly regulation. Current biology : CB 126 12445386
2011 A lateral belt of cortical LGN and NuMA guides mitotic spindle movements and planar division in neuroepithelial cells. The Journal of cell biology 123 21444683
2014 The dynamics of plant plasma membrane proteins: PINs and beyond. Development (Cambridge, England) 115 25053426
2011 LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Gαi/LGN/NuMA pathways. Molecular cell 108 21816348
2014 Par3-mInsc and Gαi3 cooperate to promote oriented epidermal cell divisions through LGN. Nature cell biology 107 25016959
2017 Cell division orientation is coupled to cell-cell adhesion by the E-cadherin/LGN complex. Nature communications 103 28045117
2002 Expression analysis and subcellular distribution of the two G-protein regulators AGS3 and LGN indicate distinct functionality. Localization of LGN to the midbody during cytokinesis. The Journal of biological chemistry 100 11832491
1996 Identification and cDNA cloning of a novel human mosaic protein, LGN, based on interaction with G alpha i2. Gene 98 8973305
2006 The parvocellular LGN provides a robust disynaptic input to the visual motion area MT. Neuron 96 16630841
2012 GPSM2 mutations cause the brain malformations and hearing loss in Chudley-McCullough syndrome. American journal of human genetics 93 22578326
2015 The Arabidopsis SWI2/SNF2 Chromatin Remodeling ATPase BRAHMA Targets Directly to PINs and Is Required for Root Stem Cell Niche Maintenance. The Plant cell 86 25991732
2004 The planar cell polarity protein Strabismus promotes Pins anterior localization during asymmetric division of sensory organ precursor cells in Drosophila. Development (Cambridge, England) 82 14701683
2014 SLK-dependent activation of ERMs controls LGN-NuMA localization and spindle orientation. The Journal of cell biology 78 24958772
2019 Cytotoxicity Evaluation of Endodontic Pins on L929 Cell Line. BioMed research international 77 31815131
2005 Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes. Proceedings of the National Academy of Sciences of the United States of America 77 16275912
2007 Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts. Proceedings of the National Academy of Sciences of the United States of America 74 17726110
2005 Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. Genes & development 74 15937221
2017 Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome. Nature communications 73 28387217
2002 Are primate lateral geniculate nucleus (LGN) cells really sensitive to orientation or direction? Visual neuroscience 73 12180863
2016 Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation. Nature structural & molecular biology 71 26751642
2007 Recovery from optic neuritis: an ROI-based analysis of LGN and visual cortical areas. Brain : a journal of neurology 68 17472983
2011 Inscuteable and NuMA proteins bind competitively to Leu-Gly-Asn repeat-enriched protein (LGN) during asymmetric cell divisions. Proceedings of the National Academy of Sciences of the United States of America 67 22171003
2006 Contribution of feedforward thalamic afferents and corticogeniculate feedback to the spatial summation area of macaque V1 and LGN. The Journal of comparative neurology 67 16871526
2017 E-cadherin and LGN align epithelial cell divisions with tissue tension independently of cell shape. Proceedings of the National Academy of Sciences of the United States of America 66 28674014
1996 No binocular rivalry in the LGN of alert macaque monkeys. Vision research 66 8711902
2021 Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans. eLife 64 34473054
2011 Structural basis for interaction between the conserved cell polarity proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN). Proceedings of the National Academy of Sciences of the United States of America 63 22074847
2019 GPSM2-GNAI Specifies the Tallest Stereocilia and Defines Hair Bundle Row Identity. Current biology : CB 57 30827920
2014 Dlg1 controls planar spindle orientation in the neuroepithelium through direct interaction with LGN. The Journal of cell biology 54 25202028
2011 Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle orientation. The Journal of cell biology 53 22024168
2006 Modulation of basal and receptor-induced GIRK potassium channel activity and neuronal excitability by the mammalian PINS homolog LGN. Neuron 53 16701207
2017 VE-Cadherin Phosphorylation Regulates Endothelial Fluid Shear Stress Responses through the Polarity Protein LGN. Current biology : CB 52 28712573
2017 ARF2 coordinates with PLETHORAs and PINs to orchestrate ABA-mediated root meristem activity in Arabidopsis . Journal of integrative plant biology 50 28074634
2017 High miR156 Expression Is Required for Auxin-Induced Adventitious Root Formation via MxSPL26 Independent of PINs and ARFs in Malus xiaojinensis. Frontiers in plant science 50 28674551
2003 Subcellular localization of LGN during mitosis: evidence for its cortical localization in mitotic cell culture systems and its requirement for normal cell cycle progression. Molecular biology of the cell 49 12925752
2002 Synaptic mechanisms regulating the activation of a Ca(2+)-mediated plateau potential in developing relay cells of the LGN. Journal of neurophysiology 49 11877491
2010 Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells. Genes, chromosomes & cancer 48 20589935
2010 Responses of the human visual cortex and LGN to achromatic and chromatic temporal modulations: an fMRI study. Journal of vision 48 21106678
2013 Evidence for dynein and astral microtubule-mediated cortical release and transport of Gαi/LGN/NuMA complex in mitotic cells. Molecular biology of the cell 45 23389635
2005 Direct binding of Lgl2 to LGN during mitosis and its requirement for normal cell division. The Journal of biological chemistry 45 15632202
1998 REM sleep deprivation in monocularly occluded kittens reduces the size of cells in LGN monocular segment. Sleep 45 9871946
1996 Rapid eye movement sleep deprivation in kittens amplifies LGN cell-size disparity induced by monocular deprivation. Brain research. Developmental brain research 44 8946054
2003 The anterogradely transported BDNF promotes retinal axon remodeling during eye specific segregation within the LGN. Molecular and cellular neurosciences 43 14697662
2005 G alpha selectivity and inhibitor function of the multiple GoLoco motif protein GPSM2/LGN. Biochimica et biophysica acta 41 15946753
2008 Cell polarity in plants: a PARspective on PINs. Current opinion in plant biology 40 18993110
2009 Drosophila GoLoco-protein Pins is a target of Galpha(o)-mediated G protein-coupled receptor signaling. Molecular biology of the cell 39 19570914
2007 A simple model of retina-LGN transmission. Journal of computational neuroscience 37 17763931
2003 Effects of relative humidity and buffer additives on the contact printing of microarrays by quill pins. Analytical biochemistry 36 12927835
2002 Organization of the feedback pathway from striate cortex (V1) to the lateral geniculate nucleus (LGN) in the owl monkey (Aotus trivirgatus). The Journal of comparative neurology 36 12442318
2003 A mouse homologue of Drosophila pins can asymmetrically localize and substitute for pins function in Drosophila neuroblasts. Journal of cell science 35 12571286
2015 Warts phosphorylates mud to promote pins-mediated mitotic spindle orientation in Drosophila, independent of Yorkie. Current biology : CB 34 26592339
2014 Receptors, repressors, PINs: a playground for strigolactone signaling. Trends in plant science 34 25037847
2002 LGN input to simple cells and contrast-invariant orientation tuning: an analysis. Journal of neurophysiology 34 12037176
2016 SAPCD2 Controls Spindle Orientation and Asymmetric Divisions by Negatively Regulating the Gαi-LGN-NuMA Ternary Complex. Developmental cell 32 26766442
2016 Pins is not required for spindle orientation in the Drosophila wing disc. Development (Cambridge, England) 32 27287805
2013 Par1b links lumen polarity with LGN-NuMA positioning for distinct epithelial cell division phenotypes. The Journal of cell biology 32 24165937
1986 The localization of cytochrome oxidase in the LGN and striate cortex of postnatal kittens. The Journal of comparative neurology 32 3003167
2015 The GPSM2/LGN GoLoco motifs are essential for hearing. Mammalian genome : official journal of the International Mammalian Genome Society 30 26662512
1982 Relationship between amblyopia, LGN cell "shrinkage" and cortical ocular dominance in cats. Experimental brain research 30 7056330
2013 Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent mitotic spindle orientation in proliferating hepatocytes. PLoS biology 29 24358023
1998 Temporal-chromatic interactions in LGN P-cells. Visual neuroscience 29 9456504
1992 Age-related expression patterns of the CD15 epitope in the human lateral geniculate nucleus (LGN). The Histochemical journal 29 1282510
1986 Differential effect of visual deprivation on cytochrome oxidase levels in major cell classes of the cat LGN. The Journal of comparative neurology 29 3007586
2018 Insc:LGN tetramers promote asymmetric divisions of mammary stem cells. Nature communications 28 29523789
2006 Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3. Biochemical and biophysical research communications 28 16458856
2001 Cartesian and non-Cartesian responses in LGN, V1, and V2 cells. Visual neuroscience 28 12020088
2014 Prevention of pin tract infection with iodine-supported titanium pins. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 27 24687211
2012 Inscuteable regulates the Pins-Mud spindle orientation pathway. PloS one 27 22253744
1998 Distinctive characteristics of subclasses of red-green P-cells in LGN of macaque. Visual neuroscience 27 9456503
1977 Lack of intralaminar sprouting of retinal axons in monkey LGN. Brain research 27 405080
2018 Manipulating Femtoliter to Picoliter Droplets by Pins for Single Cell Analysis and Quantitative Biological Assay. Analytical chemistry 26 29648445
2012 On the inscrutable role of Inscuteable: structural basis and functional implications for the competitive binding of NuMA and Inscuteable to LGN. Open biology 26 22977735
1997 On the significance of temporally structured activity in the dorsal lateral geniculate nucleus (LGN). Progress in neurobiology 26 9330424
2013 An autoinhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs. Structure (London, England : 1993) 25 23665171
1976 The effect of age on the reversibility of cellular atrophy in the LGN of the cat following monocular deprivation: a test of two hypotheses about cell growth. The Journal of comparative neurology 24 950384
2002 Modeling receptive-field structure of koniocellular, magnocellular, and parvocellular LGN cells in the owl monkey (Aotus trivigatus). Visual neuroscience 23 12688666
2012 Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Gαi. The Journal of biological chemistry 22 22952234
2011 LGN-dependent orientation of cell divisions in the dermomyotome controls lineage segregation into muscle and dermis. Development (Cambridge, England) 22 21852400
2011 Robust spindle alignment in Drosophila neuroblasts by ultrasensitive activation of pins. Molecular cell 22 21855794
2005 Interaction of transducin-alpha with LGN, a G-protein modulator expressed in photoreceptor cells. Molecular and cellular neurosciences 22 15737739
2004 Asymmetric localization of LGN but not AGS3, two homologs of Drosophila pins, in dividing human neural progenitor cells. Journal of neuroscience research 22 14994339
1988 Neural site of strabismic amblyopia in cats: X-cell acuities in the LGN. Experimental brain research 22 3234500
2011 A truncating mutation in GPSM2 is associated with recessive non-syndromic hearing loss. Clinical genetics 21 21348867