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Showing DYNLT1 — TCTEX-1 is a alias.

DYNLT1

Dynein light chain Tctex-type 1 · UniProt P63172

Length
113 aa
Mass
12.5 kDa
Annotated
2026-06-09
57 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYNLT1 (Tctex-1) is a homodimeric 14-kDa light chain of mammalian cytoplasmic dynein that functions as a cargo adaptor coupling membrane receptors and signalling proteins to the minus-end-directed microtubule motor (PMID:8943288, PMID:10399916). It is a stoichiometric, ATP-elutable component of brain cytoplasmic dynein and also assembles into flagellar inner-arm dynein (PMID:8943288, PMID:9490726). Structurally, Tctex-1 adopts a domain-swapped, dimeric fold convergent with LC8 despite lacking sequence homology, and binds a 19-residue segment of the dynein intermediate chain (DIC) bearing an R/K-R/K-X-X-R/K consensus that is shared by its cargoes (PMID:11148215, PMID:15701632, PMID:27502274). Through this hydrophobic groove it directly engages a broad set of cargoes—rhodopsin, the poliovirus receptor CD155, PTH/PTHrP receptor, BMPR-II, N- and P/Q-type Ca2+ channels, Doc2, Rab3D, and the small GTPase RagA—linking these receptors and vesicles to dynein for retrograde and polarized transport (PMID:10399916, PMID:11751937, PMID:14583445, PMID:14575690, PMID:15768038, PMID:21262767, PMID:26227614). Cargo loading is gated by phosphorylation: Ser82 phosphorylation lowers DIC affinity and ejects Tctex-1 from the motor, and a phospho-cycle is required for correct apical delivery of rhodopsin (PMID:16956385). Independently of dynein, a Gβγ-bound pool drives neurite outgrowth, and Tctex-1 antagonizes the RhoGEF Lfc to control RhoA signalling, neurogenesis, and mitotic spindle orientation (PMID:17491591, PMID:19448628, PMID:20463241). MAST4-mediated Thr94 phosphorylation recruits Tctex-1 to the ciliary transition zone to drive ciliary resorption and S-phase entry via actin dynamics and Cdc42/Rab5-dependent endocytosis (PMID:21394082, PMID:37726137). Tctex-1 also localizes to unattached kinetochores via the Ndc80 complex to ensure faithful chromosome segregation, and stabilizes mitochondrial VDAC1 against Parkin-mediated ubiquitination to support mitochondrial metabolism (PMID:25928583, PMID:37280526). Disease-linked roles include disruption of the rhodopsin interaction by retinitis pigmentosa mutations and of BMPR-II phosphorylation by primary pulmonary hypertension mutations (PMID:10399916, PMID:14583445).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 High

    Established that Tctex-1 is a genuine, stoichiometric subunit of cytoplasmic dynein rather than a loosely associated factor, defining it as part of the motor itself.

    Evidence Peptide sequencing, sucrose gradient sedimentation, ATP/GTP elution, and anti-DIC immunoprecipitation of brain dynein

    PMID:8943288

    Open questions at the time
    • Did not map the DIC contact site
    • Cargo specificity unaddressed
  2. 1998 High

    Showed the same light chain operates in both cytoplasmic and flagellar dynein across organisms, broadening its motor association beyond mammalian cytoplasm.

    Evidence Genetic/biochemical dissection of Chlamydomonas axonemal dynein and immunoblotting of sperm fractions

    PMID:9490726

    Open questions at the time
    • Functional contribution to flagellar motility not isolated
    • Relation to meiotic drive remained correlative
  3. 1999 High

    Provided the first direct cargo: Tctex-1 binds the rhodopsin C-terminal tail and links rhodopsin vesicles to dynein, establishing it as a receptor-to-motor adaptor and connecting it to retinitis pigmentosa.

    Evidence Yeast two-hybrid, pull-down, microtubule translocation assay, and rhodopsin C-terminus mutagenesis

    PMID:10399916

    Open questions at the time
    • In vivo transport requirement in photoreceptors not tested
    • Whether binding is direct to dynein-incorporated Tctex-1 vs free pool unresolved
  4. 2001 High

    Defined the molecular logic of cargo recognition by mapping the homodimeric Tctex-1 to a 19-residue DIC peptide containing an R/K-R/K-X-X-R/K motif shared with cargoes.

    Evidence NMR chemical-shift titration, gel filtration, and peptide titration

    PMID:11148215

    Open questions at the time
    • How cargo and DIC binding are coordinated not addressed
    • No high-resolution complex structure yet
  5. 2001 Medium

    Expanded the cargo repertoire to additional membrane receptors, supporting a general adaptor role rather than a rhodopsin-specific one.

    Evidence Yeast two-hybrid and co-IP mapping of CD155 SKCSR juxtamembrane motif

    PMID:11751937

    Open questions at the time
    • Retrograde neuronal transport of CD155 not directly demonstrated
    • Single lab
  6. 2005 High

    Resolved the Tctex-1 fold at high resolution, revealing convergent evolution with LC8 and a shared cargo-binding mode despite no sequence homology.

    Evidence NMR solution structure (Chlamydomonas) and 1.7 Å crystal structure (Drosophila) with comparison to LC8-nNOS

    PMID:15698565 PMID:15701632

    Open questions at the time
    • Mammalian DIC-bound structure not yet solved
    • Functional consequence of fold for specificity inferred, not tested
  7. 2006 High

    Identified Ser82 phosphorylation as a switch that ejects Tctex-1 from dynein without disturbing cargo binding, establishing a phospho-gated assembly/disassembly cycle needed for cargo delivery.

    Evidence Phosphomimetic S82E/S82A mutagenesis, velocity sedimentation, co-IP, and rhodopsin localization in polarized MDCK cells

    PMID:16956385

    Open questions at the time
    • Kinase responsible for Ser82 not identified
    • Spatiotemporal regulation of the cycle unknown
  8. 2007 High

    Revealed a dynein-independent function: Gβγ competes with DIC to capture a free Tctex-1 pool that drives neurite outgrowth, separating motor adaptor and signalling roles.

    Evidence Co-IP from embryonic brain, sucrose gradient fractionation, and neurite outgrowth assays in hippocampal neurons

    PMID:17491591

    Open questions at the time
    • Downstream effectors of the Gβγ-Tctex-1 complex incomplete
    • How the two pools are partitioned in vivo unclear
  9. 2009 High

    Placed Tctex-1 in a neurogenic signalling pathway as a negative regulator of the RhoGEF Lfc, controlling spindle orientation and the balance between precursor cycling and neurogenesis.

    Evidence shRNA knockdown in vitro and by in utero electroporation, BrdU/EdU labeling, spindle measurement, and double-knockdown epistasis

    PMID:19448628

    Open questions at the time
    • Whether this role requires dynein or the free pool unresolved at this stage
    • Direct biochemical Lfc interaction shown later
  10. 2010 Medium

    Mechanistically grounded the Lfc antagonism by showing Tctex-1 directly binds Lfc, inhibits its GEF activity, and lowers RhoA-GTP to promote axon formation.

    Evidence Co-IP, RhoA GTP pull-down activity assay, co-localization, and axon formation assays in neurons

    PMID:20463241

    Open questions at the time
    • Structural basis of Lfc inhibition unknown
    • Single lab
  11. 2011 High

    Identified a second regulatory phosphosite, Thr94, whose modification recruits Tctex-1 to the ciliary transition zone to couple ciliary disassembly with cell-cycle progression via actin dynamics.

    Evidence Phospho-specific antibody, T94E/T94A mutants, siRNA, S-phase and cilia-length assays, and in vivo cortical progenitor analysis

    PMID:21394082

    Open questions at the time
    • Thr94 kinase unidentified at this stage
    • Mechanistic link to actin not fully defined
  12. 2011 Medium

    Extended adaptor function to GTP-dependent vesicular cargo by linking Rab3D-bearing vesicles to dynein, required for osteoclast bone resorption.

    Evidence Yeast two-hybrid, GTP-dependent co-IP, immunofluorescence, siRNA, and bone resorption pit assay

    PMID:21262767

    Open questions at the time
    • Direct transport of Rab3D vesicles by dynein not visualized in real time
    • Single lab
  13. 2013 Medium

    Connected Tctex-1 to mitochondrial regulation and microtubule stability, with Ser82 phosphorylation aggravating hypoxic permeability transition through increased free tubulin.

    Evidence VDAC1 co-IP, S82E/S82A adenoviral expression, mitochondrial potential/ATP/cytochrome c assays, tubulin fractionation in cardiomyocytes

    PMID:12009301 PMID:22164227 PMID:24170091

    Open questions at the time
    • Whether VDAC1 effect is dynein-dependent unclear
    • Mechanism linking S82 to tubulin not defined
  14. 2013 Medium

    Revealed a nuclear-periphery role: Tctex-1 binds FG-repeat nucleoporins and NUP98-HOXA9 to support oncogenic transcription and hematopoietic proliferation.

    Evidence Yeast two-hybrid, pull-down, co-IP, deletion mapping, RNAi, reporter and proliferation assays, immunofluorescence

    PMID:23840580

    Open questions at the time
    • Whether this is dynein-dependent unknown
    • Physiological relevance beyond leukemic context untested
  15. 2015 Medium

    Demonstrated dynein-independent kinetochore function: Tctex-1 localizes to unattached kinetochores via the Ndc80 complex (not the ZW10-dynein pathway) and is needed for accurate chromosome segregation.

    Evidence siRNA, kinetochore-marker immunofluorescence, time-lapse, segregation assays, epistasis with ZW10 and Ndc80 depletion

    PMID:25928583

    Open questions at the time
    • Molecular role at the kinetochore unresolved
    • Single lab
  16. 2015 Medium

    Showed Tctex-1 can simultaneously engage DIC and a second ligand (RagA) at distinct surfaces, supporting a tripartite cargo-loading architecture and pathogen hijacking via the same recognition motif.

    Evidence NMR residue-level mapping of separate DIC and RagA sites; yeast two-hybrid and motif mutagenesis of Chlamydia CT850

    PMID:25944661 PMID:26227614

    Open questions at the time
    • Functional output of RagA-Tctex-1-dynein complex unclear
    • In vivo simultaneous occupancy not shown
  17. 2016 High

    Defined the recognition code of the canonical binding groove and solved the mammalian DYNLT1-DIC complex, formalizing Tctex-1 as a dimerization engine with a dual cargo-binding mode.

    Evidence Pepscan positional mutagenesis and NMR solution structure of the human DYNLT1-DIC complex

    PMID:27502274

    Open questions at the time
    • How phosphorylation alters groove engagement structurally not resolved
    • Single lab
  18. 2018 High

    Linked Tctex-1 to actin-based epithelial morphogenesis by controlling desmosomal Dsg1 compartmentalization and perijunctional actin polymerization during keratinocyte delamination.

    Evidence Co-IP, RNAi, FRAP, traction force microscopy, and live imaging

    PMID:29535305

    Open questions at the time
    • Whether dynein is required not established
    • Connection to the Gβγ/cytoskeletal pool not tested
  19. 2018 Medium

    Showed Thr94 phosphorylation gates a receptor interaction (KIM-1) whose actin/microtubule-dependent dissociation drives efferocytosis, generalizing phospho-regulated cargo release.

    Evidence Yeast two-hybrid, co-IP dissociation kinetics, shRNA, efferocytosis assays, T94E mutant binding

    PMID:29693725

    Open questions at the time
    • Kinase/phosphatase controlling T94 in this context not defined
    • Single lab
  20. 2023 High

    Identified MAST4 as the Thr94 kinase, completing the upstream regulation of ciliary resorption through Cdc42 activation and Rab5-mediated periciliary endocytosis.

    Evidence Kinase-dead MAST4 mutants, co-IP with the kinase domain, phospho-specific immunofluorescence, Cdc42 and Rab5 functional assays

    PMID:37726137

    Open questions at the time
    • Upstream signals activating MAST4 unclear
    • Ser82 kinase still unidentified
  21. 2023 Medium

    Provided a mechanism for the mitochondrial role by showing DYNLT1 stabilizes VDAC1 by blocking Parkin-mediated ubiquitination, promoting metabolism and tumor growth.

    Evidence Co-IP, ubiquitination assay, mitochondrial potential/ATP measurement, shRNA/overexpression, and xenografts

    PMID:37280526

    Open questions at the time
    • How DYNLT1 binding occludes Parkin not structurally defined
    • Single lab
  22. 2025 Medium

    Provided in vivo loss-of-function evidence: DYNLT1 knockout mice develop atrial fibrillation via TMCO1 mislocalization and ER calcium overload, tying the protein to cardiac homeostasis.

    Evidence CRISPR/Cas9 knockout mice, ECG/echocardiography, mass spectrometry, and TMCO1/gap-junction immunofluorescence

    PMID:40457945

    Open questions at the time
    • Whether TMCO1 mislocalization is a direct dynein-transport defect untested
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the two regulatory phosphosites, distinct cargo classes, and the dynein-bound versus free pools are coordinately switched in a single cell to dictate cargo loading versus signalling remains unresolved.
  • No unified structural model of phospho-gated DIC versus cargo occupancy
  • Ser82 kinase unidentified
  • Quantitative rules partitioning dynein-bound and Gβγ-bound pools in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 3 GO:0005856 cytoskeleton 2 GO:0005929 cilium 2 GO:0005635 nuclear envelope 1 GO:0005694 chromosome 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2
Partners
BMPR2DYNC1I (DYNEIN INTERMEDIATE CHAIN)GNB/GNG (GΒΓ)LFC/ARHGEF2MAST4RAGARHO (RHODOPSIN)VDAC1
Complex memberships
cytoplasmic dynein complexflagellar inner-arm dynein I1

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 DYNLT1 (Tctex-1) is a stoichiometric 14-kDa light chain component of mammalian brain cytoplasmic dynein, co-sedimenting with microtubules, eluting with ATP (but not GTP), and immunoprecipitated by anti-dynein intermediate chain antibody. Peptide sequencing, sucrose density gradient sedimentation, ATP/GTP elution assays, immunoprecipitation with anti-intermediate chain monoclonal antibody The Journal of biological chemistry High 8943288
1998 Tctex-1 is present not only in cytoplasmic dynein but also in Chlamydomonas flagellar inner dynein arm I1 and in mouse sperm, supporting a role in flagellar dynein function relevant to meiotic drive. Genetic and biochemical dissection of Chlamydomonas flagellar axoneme, immunoblotting of fractionated dynein complexes The Journal of cell biology High 9490726
1999 Tctex-1 binds directly to the C-terminal cytoplasmic tail of rhodopsin, mediating dynein-dependent transport of rhodopsin-bearing vesicles along microtubules; retinitis pigmentosa-causing C-terminal rhodopsin mutations disrupt this interaction. In vitro pull-down assays, yeast two-hybrid, microtubule translocation assay, site-directed mutagenesis of rhodopsin C-terminus Cell High 10399916
1998 Tctex-1 specifically interacts with the Src-family kinase p59fyn via the first 19 amino acids of Fyn (requiring two lysine residues), and co-localizes with Fyn at the cleavage furrow and mitotic spindles during cytokinesis in T cell hybridomas. Yeast two-hybrid cloning, GST pull-down from cell lysates, immunofluorescence confocal microscopy Journal of immunology Medium 9712037
1998 Tctex-1 interacts with Doc2α and Doc2β in cell-free and intact cell systems; overexpression of the Doc2 Tctex-1-binding domain alters intracellular localization of mannose 6-phosphate receptor and cathepsin D, implicating Tctex-1 in dynein-dependent vesicle transport from trans-Golgi network to late endosomes. Co-immunoprecipitation, GST pull-down, overexpression with subcellular localization of cargoes by immunofluorescence The Journal of biological chemistry Medium 9804756
2001 Tctex-1 forms a homodimer in solution and binds directly to a 19-residue fragment of the dynein intermediate chain (DIC) immediately following the second alternative splicing site; the DIC-binding peptide contains an R/K-R/K-X-X-R/K consensus motif shared by diverse Tctex-1 cargo proteins. NMR spectroscopy (backbone secondary structure, chemical shift titration), gel filtration, peptide titration assays The Journal of biological chemistry High 11148215
2001 The cytoplasmic domain of poliovirus receptor CD155 associates with Tctex-1 via a SKCSR motif in the juxtamembrane region, confirmed biochemically and by co-immunoprecipitation, suggesting Tctex-1 links CD155-containing endocytic vesicles to the dynein motor for retrograde neuronal transport. Yeast two-hybrid, co-immunoprecipitation, domain mapping by deletion/site-directed mutagenesis The Journal of biological chemistry Medium 11751937
2001 Tctex-1/Tctex2 family light chains exist as dimers (Tctex1) or monomers (Tctex2) in solution; Chlamydomonas Tctex1 dimerizes in vivo as shown by yeast two-hybrid; cross-linking of outer arm dynein reveals interaction of Tctex2 (LC2) with LC6. Gel filtration, native gel electrophoresis, yeast two-hybrid, chemical cross-linking with dimethylpimelimidate, immunoblotting The Journal of biological chemistry Medium 11278908
2002 DYNLT1 (Tctex-1) interacts with VDAC1 in vivo and in vitro; this interaction alters the electrophysiological properties of VDAC1 in planar lipid bilayer experiments (rTctex-1 slightly increases voltage-dependence of hVDAC1); the two proteins co-localize in HeLa cells. Sos-recruitment yeast two-hybrid, overlay assay with recombinant proteins, indirect immunofluorescence, EGFP fusion co-localization, planar lipid bilayer electrophysiology The international journal of biochemistry & cell biology Medium 12009301
2003 Tctex-1 interacts with the cytoplasmic tail of BMPR-II in an isoform-specific manner and is phosphorylated by BMPR-II; primary pulmonary hypertension-causing mutations in exon 12 of BMPR2 disrupt this phosphorylation. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis of BMPR-II, co-localization by immunofluorescence Human molecular genetics Medium 14583445
2003 Tctex-1 interacts directly with the COOH-terminal tail of the PTH/PTH-related protein receptor (PTHR); a bipartite 34-amino-acid binding motif in PTHR is required, and a GFP-fused PTHR mutant impaired in Tctex-1 binding shows decreased internalization rate in response to PTH in MDCK cells. Yeast two-hybrid, in vitro binding assay, site-directed mutagenesis of PTHR, internalization assay by live imaging in MDCK cells Biochemical and biophysical research communications Medium 14575690
2004 HSV-1 outer capsid protein VP26 binds dynein light chains Tctex-1 and RP3; VP26+ capsids microinjected into cells co-localize with Tctex-1 and microtubules and move toward the nucleus, whereas VP26− capsids do not, demonstrating VP26-mediated retrograde dynein-dependent transport. Yeast two-hybrid, in vitro pull-down, microinjection of recombinant capsids into live cells, fluorescence microscopy The Journal of biological chemistry High 15117959
2005 NMR solution structure of the Chlamydomonas Tctex1 dimer reveals a strand-switched beta-sheet interface similar to LC8; structural analysis identifies the dynein intermediate chain binding site and predicts a mechanism for cargo attachment distinct from but convergent with LC8. NMR solution structure determination, structural comparison with LC8 Structure High 15698565
2005 Crystal structure of Drosophila TcTex-1 at 1.7 Å reveals a homodimeric domain-swapped fold nearly identical to LC8 despite no sequence homology; the N-terminus binds a crystallographic dimer as an antiparallel beta-strand at the same position as nNOS in LC8, suggesting TcTex-1 binds targets similarly to LC8. X-ray crystallography (MAD phasing, 1.7 Å), structural comparison with LC8-nNOS complex The Journal of biological chemistry High 15701632
2005 Tctex-1 interacts directly and selectively with N- and P/Q-type (but not L-type) voltage-gated Ca2+ channels; overexpression of the channel fragment containing the Tctex-1 binding domain in hippocampal neurons decreases surface expression of N- and P/Q-type channels and reduces Ca2+ current density. Co-immunoprecipitation, overexpression with immunostaining for surface channel levels, electrophysiology (Ca2+ current density measurement) in hippocampal neurons Nature neuroscience Medium 15768038
2006 Phosphorylation of Tctex-1 at Ser82 (mimicked by S82E mutant) reduces its affinity for dynein intermediate chain without affecting rhodopsin binding, preventing incorporation into the dynein complex; S82E dominant-negative and S82A (dephospho-mimic) both cause mislocalization of rhodopsin in polarized MDCK cells, indicating that a phosphorylation-dependent assembly/disassembly cycle of Tctex-1 from dynein is required for apical cargo delivery. Velocity sedimentation, co-immunoprecipitation, phosphomimetic mutagenesis (S82E, S82A), immunofluorescence in polarized MDCK cells Traffic High 16956385
2006 Tctex-1 dimerization is obligatorily coupled to folding; unfolding follows a two-state mechanism (folded dimer → 2 unfolded monomers) with no stable monomeric intermediate, distinguishing it mechanistically from LC8 which shows a three-state mechanism. Equilibrium unfolding monitored by intrinsic fluorescence intensity, fluorescence anisotropy, circular dichroism; sedimentation equilibrium; chemical cross-linking Biochemistry Medium 16734416
2007 Gβγ binds Tctex-1 and competes with dynein intermediate chain for binding, segregating a dynein-free pool of Tctex-1; this Gβγ-Tctex-1 complex is endogenous in embryonic mouse brain and promotes neurite outgrowth independently of dynein. Co-immunoprecipitation from embryonic brain extracts, sucrose gradient fractionation, overexpression/dominant-negative studies in primary hippocampal neurons, neurite outgrowth assay The EMBO journal High 17491591
2008 Tctex-1 mediates intracellular targeting of Mason-Pfizer monkey virus (M-PMV) matrix protein to a cytoplasmic assembly site; a single amino acid mutation (R55F) in MA buries the putative Tctex-1 binding motif, redirecting viral assembly from cytoplasm to plasma membrane. In vitro biochemical binding assays, NMR structure comparison of wt and R55F MA, mutagenesis Proceedings of the National Academy of Sciences of the United States of America Medium 18647839
2009 Tctex-1 (Dynlt1) acts as a negative regulator of Lfc (Arhgef2, a RhoGEF) in cortical neural precursors; Dynlt1 knockdown promotes neurogenesis and depletes cycling radial precursors, while Arhgef2 knockdown inhibits neurogenesis; double knockdown epistasis shows Tctex-1 antagonizes Lfc's proneurogenic actions and the two proteins regulate mitotic spindle orientation. shRNA knockdown in cortical precursors in culture and in utero electroporation, BrdU/EdU labeling, spindle orientation measurement, genetic epistasis (double knockdown) Nature neuroscience High 19448628
2010 Tctex-1 co-localizes and physically interacts with Lfc in neurons, inhibiting Lfc's GEF activity, decreasing Rho-GTP levels, and antagonizing Lfc-mediated inhibition of axon formation; this places Tctex-1 upstream of RhoA in neuronal polarization. Co-immunoprecipitation, RhoA activity assay (GTP-Rho pull-down), fluorescence co-localization, genetic knockdown, axon formation assay The Journal of neuroscience Medium 20463241
2011 Phospho-Thr94 Tctex-1 is recruited to ciliary transition zones prior to S-phase entry and drives both ciliary disassembly and cell cycle progression; phosphomimetic T94E accelerates cilium disassembly and S-phase entry; this function requires actin dynamics and is dispensable in non-ciliated cells. Phospho-specific antibody, phosphomimetic (T94E) and phospho-dead (T94A) mutant expression, siRNA knockdown, S-phase entry assay (BrdU), cilia length measurement, actin perturbation experiments, in vivo cortical neural progenitor analysis Nature cell biology High 21394082
2011 Tctex-1 interacts with Rab3D in a GTP-dependent manner, co-occupies Rab3D vesicles in osteoclasts, associates with dynein and microtubules, and is required for bone resorption; Tctex-1 RNAi significantly impairs resorption capacity and mislocalizes Rab3D vesicles. Yeast two-hybrid, co-immunoprecipitation, GTP-dependence assay, immunofluorescence, siRNA knockdown, bone resorption pit assay Molecular and cellular biology Medium 21262767
2011 DYNLT1 interacts with VDAC1, and DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization; DYNLT1 co-immunoprecipitates with VDAC1 and is closely associated with microtubules and VDAC1 by immunofluorescence in cardiomyocytes. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, siRNA knockdown, mitochondrial membrane potential and ATP assays PloS one Medium 22164227
2013 Phosphorylation of DYNLT1 at Ser82 (S82E phosphomimetic) in hypoxia aggravates mitochondrial permeability transition and increases free tubulin (destabilizing microtubules), while S82A (dephospho-mimic) diminishes hypoxia-induced injury, demonstrating a regulatory role for S82 phosphorylation in microtubule stability and mitochondrial protection. Recombinant adenovirus expression of S82E and S82A mutants, mitochondrial membrane potential assay, cytochrome c release, ATP quantification, free/polymerized tubulin fractionation Molecules and cells Medium 24170091
2013 DYNLT1 interacts with NUP98-HOXA9 (via the FG-repeat region) and with wild-type NUP98 and other FG-repeat nucleoporins; DYNLT1 knockdown reduces NUP98-HOXA9-dependent transcriptional activation and inhibits NUP98-HOXA9-induced proliferation of CD34+ hematopoietic cells; DYNLT1 localizes to the nuclear periphery co-localizing with nuclear pore complexes. Yeast two-hybrid, in vitro pull-down, co-immunoprecipitation, deletion mapping, RNAi knockdown, transcription reporter assay, hematopoietic cell proliferation assay, immunofluorescence PloS one Medium 23840580
2015 C. trachomatis inclusion membrane protein CT850 interacts with DYNLT1 via an R/K-R/K-X-X-R/K motif; CT850 localizes to the MTOC in a DYNLT1-binding-domain-dependent manner; DYNLT1 is enriched at CT850 foci on the inclusion membrane; depletion of DYNLT1 disrupts inclusion association with centrosomes. Yeast two-hybrid screen, co-localization by immunofluorescence, site-directed mutagenesis of CT850 binding motif, siRNA knockdown of DYNLT1 Biochemical and biophysical research communications Medium 25944661
2015 Tctex-1 associates with unattached kinetochores independently of dynein; Tctex-1 knockdown causes prolonged mitotic arrest and chromosome missegregation; kinetochore localization requires the Ndc80 complex but not the ZW10-dynein pathway; Tctex-1 knockdown does not affect dynein localization or function at the kinetochore. siRNA knockdown, immunofluorescence for kinetochore markers, time-lapse microscopy, chromosome segregation assay, epistasis with ZW10 and Ndc80 complex depletion Cell cycle Medium 25928583
2015 DYNLT1 forms a tripartite complex with dynein intermediate chain and RagA; NMR spectroscopy distinguishes the DIC-binding residues on DYNLT1 from the RagA-binding residues; a β-strand within the RagA G3 box mediates association with DYNLT1. NMR spectroscopy (residue-level mapping of binding sites), yeast two-hybrid, pull-down assays The FEBS journal Medium 26227614
2016 The hydrophobic groove of DYNLT1 accommodates dynein intermediate chain and diverse cargo peptides; pepscan mutagenesis defines the consensus recognition sequence for the canonical binding groove; NMR structure of human DYNLT1 in complex with dynein intermediate chain is determined; DYNLT1 functions as a molecular dimerization engine; evidence for a dual binding mode for Lfc and PTHR. Pepscan (positional scanning mutagenesis), NMR spectroscopy (solution structure of mammalian DYNLT1-DIC complex), biochemical binding assays The Journal of biological chemistry High 27502274
2018 Desmoglein 1 (Dsg1) interacts with Tctex-1 and cortactin; Tctex-1 ensures correct membrane compartmentalization of Dsg1-containing desmosomes, enabling cortactin/Arp2/3-dependent perijunctional actin polymerization and decreased E-cadherin tension, thereby promoting keratinocyte delamination during epidermal stratification. Co-immunoprecipitation, RNAi knockdown, live imaging, FRAP, traction force microscopy, immunofluorescence, overexpression in simple epithelial cells Nature communications High 29535305
2018 Tctex-1 interacts with KIM-1 at baseline but dissociates within 90 min of efferocytosis initiation; this dissociation requires actin and microtubule polymerization; Tctex-1 knockdown inhibits efferocytosis comparably to KIM-1 knockdown; KIM-1 expression inhibits phosphorylation of Tctex-1 at T94, and the T94E phosphomimetic shows reduced binding to KIM-1. Yeast two-hybrid, co-immunoprecipitation, confocal imaging, shRNA knockdown, efferocytosis assay, pharmacological disruption of cytoskeleton Journal of cellular physiology Medium 29693725
2020 Exosomal miR-15b-3p targets DYNLT1 mRNA (confirmed by dual-luciferase reporter), suppressing DYNLT1 expression and downstream Caspase-9 and Caspase-3, thereby inhibiting apoptosis and promoting gastric cancer cell migration, invasion and proliferation in vitro and tumor growth in vivo. Dual-luciferase reporter assay, Western blotting, qRT-PCR, exosome transfer with PKH26/GFP-CD63 labeling, xenograft tumor models Journal of experimental & clinical cancer research Medium 32039741
2020 Tctex-1 augments PTHR-mediated Gs/adenylyl cyclase signaling by directly binding adenylyl cyclase type 6 (AC6) and activating AC independently of its binding to PTHR. Co-immunoprecipitation (Tctex-1 with AC6), cAMP assay in cells expressing Tctex-1 with/without PTHR, dominant-negative and overexpression approaches Journal of pharmacological sciences Medium 33357773
2023 DYNLT1 co-localizes with VDAC1 on mitochondria and stabilizes VDAC1 by inhibiting E3 ligase Parkin-mediated ubiquitination and degradation of VDAC1, thereby promoting mitochondrial metabolism (membrane potential, ATP production) and breast cancer cell proliferation/invasion in vitro and tumor development in vivo. Co-immunoprecipitation, ubiquitination assay, mitochondrial membrane potential measurement, ATP quantification, in vivo xenograft, shRNA knockdown and overexpression Molecular medicine Medium 37280526
2023 MAST4 kinase localizes to the primary cilium, binds the kinase domain of Tctex-1, and phosphorylates Tctex-1 at Thr94; MAST4 suppression blocks serum-induced ciliary resorption and phospho-(T94)Tctex-1 recruitment to the ciliary base; MAST4 is required for Cdc42 activation and Rab5-mediated periciliary membrane endocytosis during ciliary resorption. siRNA/shRNA knockdown, overexpression of catalytic-dead MAST4 mutants, phospho-specific immunofluorescence, co-immunoprecipitation (Tctex-1 with MAST4 kinase domain), Cdc42 activation assay, Rab5 endocytosis assay Life science alliance High 37726137
2025 DYNLT1 knockout in mice (CRISPR/Cas9) induces spontaneous atrial fibrillation associated with reduced TMCO1 distribution in the ER of atrial cardiomyocytes, leading to ER calcium overload; DYNLT1 deletion also causes downregulation of gap junction proteins and increased cardiomyocyte apoptosis. CRISPR/Cas9 knockout mice, electrocardiography, echocardiography, histology, mass spectrometry, immunofluorescence for TMCO1 and gap junction proteins Biology open Medium 40457945
2025 Quantitative ITC combined with Bayesian inference of a seven-state binding model reveals that Tctex-1 and LC8 display opposing cooperativities (positive and negative) in assembling with the dynein intermediate chain, and identifies previously inaccessible half-bound states that may regulate dynein cargo attachment and release. Isothermal titration calorimetry (39 experiments), hierarchical Bayesian inference, global thermodynamic modeling of IC/LC8/Tctex-1 assembly bioRxivpreprint Medium bio_10.1101_2025.07.14.664506

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Rhodopsin's carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1. Cell 413 10399916
2011 Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nature cell biology 193 21394082
2002 Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light chain Tctex1 and the heat-shock protein PBP74. The international journal of biochemistry & cell biology 132 12009301
2004 Herpes simplex virus type 1 capsid protein VP26 interacts with dynein light chains RP3 and Tctex1 and plays a role in retrograde cellular transport. The Journal of biological chemistry 129 15117959
1996 The mouse t-complex-encoded protein Tctex-1 is a light chain of brain cytoplasmic dynein. The Journal of biological chemistry 116 8943288
2001 Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesis. The Journal of biological chemistry 115 11751937
1998 Identification of the t complex-encoded cytoplasmic dynein light chain tctex1 in inner arm I1 supports the involvement of flagellar dyneins in meiotic drive. The Journal of cell biology 104 9490726
2003 Functional interaction between BMPR-II and Tctex-1, a light chain of Dynein, is isoform-specific and disrupted by mutations underlying primary pulmonary hypertension. Human molecular genetics 103 14583445
2020 Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer. Journal of experimental & clinical cancer research : CR 97 32039741
1989 tctex-1: a candidate gene family for a mouse t complex sterility locus. Cell 94 2570638
2001 Structure of Tctex-1 and its interaction with cytoplasmic dynein intermediate chain. The Journal of biological chemistry 92 11148215
2009 Lfc and Tctex-1 regulate the genesis of neurons from cortical precursor cells. Nature neuroscience 75 19448628
1998 Interaction of p59fyn kinase with the dynein light chain, Tctex-1, and colocalization during cytokinesis. Journal of immunology (Baltimore, Md. : 1950) 63 9712037
1998 Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein. Implication in dynein-dependent vesicle transport. The Journal of biological chemistry 60 9804756
2001 The Tctex1/Tctex2 class of dynein light chains. Dimerization, differential expression, and interaction with the LC8 protein family. The Journal of biological chemistry 59 11278908
1994 Identification of a gene from Xp21 with similarity to the tctex-1 gene of the murine t complex. Human molecular genetics 59 8004092
2007 G protein beta gamma subunit interaction with the dynein light-chain component Tctex-1 regulates neurite outgrowth. The EMBO journal 58 17491591
2018 Desmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination. Nature communications 53 29535305
2015 Chlamydia trachomatis inclusion membrane protein CT850 interacts with the dynein light chain DYNLT1 (Tctex1). Biochemical and biophysical research communications 47 25944661
2005 Solution structure of the Tctex1 dimer reveals a mechanism for dynein-cargo interactions. Structure (London, England : 1993) 46 15698565
2003 PTH/PTH-related protein receptor interacts directly with Tctex-1 through its COOH terminus. Biochemical and biophysical research communications 43 14575690
2005 Crystal structure of dynein light chain TcTex-1. The Journal of biological chemistry 38 15701632
2006 Regulatory dissociation of Tctex-1 light chain from dynein complex is essential for the apical delivery of rhodopsin. Traffic (Copenhagen, Denmark) 34 16956385
2008 D-retrovirus morphogenetic switch driven by the targeting signal accessibility to Tctex-1 of dynein. Proceedings of the National Academy of Sciences of the United States of America 33 18647839
2010 Evidence for the involvement of Lfc and Tctex-1 in axon formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 32 20463241
2011 Tctex-1, a novel interaction partner of Rab3D, is required for osteoclastic bone resorption. Molecular and cellular biology 31 21262767
2004 Testis-specific human small heat shock protein HSPB9 is a cancer/testis antigen, and potentially interacts with the dynein subunit TCTEL1. European journal of cell biology 30 15503857
2011 The interaction of flavivirus M protein with light chain Tctex-1 of human dynein plays a role in late stages of virus replication. Virology 29 21767858
2011 MAP4 mechanism that stabilizes mitochondrial permeability transition in hypoxia: microtubule enhancement and DYNLT1 interaction with VDAC1. PloS one 29 22164227
1996 Cloning, expression, and mapping of TCTEL1, a putative human homologue of murine Tcte1, to 6q. Cytogenetics and cell genetics 29 8646886
1995 Identification of a germ-cell-specific transcriptional repressor in the promoter of Tctex-1. Development (Cambridge, England) 27 7768192
2011 Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1. Biochemical and biophysical research communications 25 21835165
2005 A tctex1-Ca2+ channel complex for selective surface expression of Ca2+ channels in neurons. Nature neuroscience 25 15768038
1998 A dynein light chain of sea urchin sperm flagella is a homolog of mouse Tctex 1, which is encoded by a gene of the t complex sterility locus. Gene 24 9602174
1998 Identification of a dynein molecular motor component in Torpedo electroplax; binding and phosphorylation of Tctex-1 by Fyn. FEBS letters 17 9762924
2015 Aberrant Expression of Dynein light chain 1 (DYNLT1) is Associated with Human Male Factor Infertility. Molecular & cellular proteomics : MCP 16 26432663
2023 DYNLT1 promotes mitochondrial metabolism to fuel breast cancer development by inhibiting ubiquitination degradation of VDAC1. Molecular medicine (Cambridge, Mass.) 13 37280526
2013 Phosphorylation of DYNLT1 at serine 82 regulates microtubule stability and mitochondrial permeabilization in hypoxia. Molecules and cells 13 24170091
2015 A dynein independent role of Tctex-1 at the kinetochore. Cell cycle (Georgetown, Tex.) 12 25928583
2010 Identification of the Tctex-1 regulatory element that directs expression to neural stem/progenitor cells in developing and adult brain. The Journal of comparative neurology 12 20575070
2019 Relationship between DYNLT1 and Beclin1 expression and the fertilising potential of human spermatozoa. Andrologia 11 31382319
2015 DYNLT (Tctex-1) forms a tripartite complex with dynein intermediate chain and RagA, hence linking this small GTPase to the dynein motor. The FEBS journal 11 26227614
2006 Folding is coupled to dimerization of Tctex-1 dynein light chain. Biochemistry 11 16734416
2016 Molecular Basis for the Protein Recognition Specificity of the Dynein Light Chain DYNLT1/Tctex1: CHARACTERIZATION OF THE INTERACTION WITH ACTIVIN RECEPTOR IIB. The Journal of biological chemistry 10 27502274
2023 MAST4 promotes primary ciliary resorption through phosphorylation of Tctex-1. Life science alliance 8 37726137
2018 Tctex-1, a novel interaction partner of Kidney Injury Molecule-1, is required for efferocytosis. Journal of cellular physiology 8 29693725
2017 MAP6 interacts with Tctex1 and Cav 2.2/N-type calcium channels to regulate calcium signalling in neurons. The European journal of neuroscience 8 29094416
2013 Dynein Light Chain 1 (DYNLT1) Interacts with Normal and Oncogenic Nucleoporins. PloS one 8 23840580
2018 MAP4 regulates Tctex-1 and promotes the migration of epidermal cells in hypoxia. Experimental dermatology 7 30091292
2015 Cannabinoid receptor 2 expression modulates Gβ(1)γ(2) protein interaction with the activator of G protein signalling 2/dynein light chain protein Tctex-1. Biochemical pharmacology 7 26410677
2023 Identification of DYNLT1 associated with proliferation, relapse, and metastasis in breast cancer. Frontiers in medicine 6 37081842
2018 Structure based function-annotation of hypothetical protein MGG_01005 from Magnaporthe oryzae reveals it is the dynein light chain orthologue of dynlt1/3. Scientific reports 5 29500373
2020 Tctex-1 augments G protein-coupled receptor-mediated Gs signaling by activating adenylyl cyclase. Journal of pharmacological sciences 3 33357773
2017 Tctex1 plays a key role in the α-synuclein autophagy lysosomal degradation pathway. Neuroscience letters 2 28970129
2025 Generation and characterization of a DYNLT1-knockout mouse model reveals electrophysiological alterations and potential mechanistic contributors to atrial fibrillation. Biology open 1 40457945
2018 Silencing of Tctex1 impairs autophagy lysosomal degradation of α-synuclein and cell viability. Neuroreport 1 29406369
2007 Characterization of a Novel DNA Motif in the Tctex1 and TCP10 Gene Complexes and its Prevalence in the Mouse Genome. Advances in biological research 1 20514145

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