Affinage

DYNLT1

Dynein light chain Tctex-type 1 · UniProt P63172

Length
113 aa
Mass
12.5 kDa
Annotated
2026-04-28
57 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYNLT1 (Tctex-1) is a homodimeric light chain of both cytoplasmic and flagellar dynein that functions as a versatile cargo adaptor linking diverse transmembrane receptors and vesicular cargoes to the retrograde microtubule motor, while also performing dynein-independent roles in actin regulation, ciliary resorption, kinetochore–microtubule attachment, and mitochondrial homeostasis. As a dynein subunit, DYNLT1 binds the dynein intermediate chain via a hydrophobic groove and recruits cargoes including rhodopsin, CD155, BMPR-II, PTHR, N/P/Q-type Ca²⁺ channels, Rab3D, RagA, and viral proteins (HSV-1 VP26, M-PMV matrix, flavivirus prM/M, Chlamydia CT850) through recognition motifs that engage overlapping or distinct surfaces on the DYNLT1 dimer (PMID:10399916, PMID:11751937, PMID:15117959, PMID:26227614, PMID:27502274). Phosphorylation at S82 releases DYNLT1 from the dynein complex to regulate apical cargo delivery, while MAST4-mediated phosphorylation at T94 recruits DYNLT1 to the ciliary transition zone to drive ciliary disassembly and cell-cycle re-entry via Cdc42 activation and actin remodeling (PMID:16956385, PMID:21394082, PMID:37726137). Independent of dynein, DYNLT1 promotes neurite outgrowth by competing with Gβγ for intermediate-chain binding and antagonizes the Rho-GEF Lfc to control cortical neurogenesis, localizes to kinetochores via Ndc80 to ensure chromosome alignment, facilitates keratinocyte delamination through cortactin/Arp2/3-dependent actin polymerization at desmosomes, and stabilizes mitochondrial VDAC1 by blocking Parkin-mediated ubiquitination (PMID:17491591, PMID:19448628, PMID:25928583, PMID:29535305, PMID:37280526).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1996 High

    The molecular identity of DYNLT1 as a bona fide dynein subunit was established, resolving whether the t-complex-encoded Tctex-1 protein had a direct role in the motor complex.

    Evidence Co-sedimentation with microtubules and co-immunoprecipitation with dynein intermediate chain from mammalian brain

    PMID:8943288

    Open questions at the time
    • Stoichiometry within the dynein complex not yet determined
    • Cargo-adaptor function not yet tested
  2. 1998 High

    DYNLT1 was shown to be a shared component of both cytoplasmic and flagellar (axonemal inner arm I1) dynein, linking the t-haplotype meiotic drive phenotype to flagellar motor dysfunction.

    Evidence Genetic and biochemical dissection of Chlamydomonas axonemal dynein mutants

    PMID:9490726

    Open questions at the time
    • Mechanism by which Tctex-1 dysfunction causes meiotic drive not resolved
    • Whether cytoplasmic and axonemal binding modes differ
  3. 1999 High

    The cargo-adaptor paradigm for DYNLT1 was established when it was shown to directly bind the rhodopsin cytoplasmic tail and mediate vesicular transport along microtubules, with retinitis pigmentosa mutations disrupting this interaction.

    Evidence Co-IP, pull-down, microtubule motility assay, and mutagenesis of rhodopsin C-terminal tail

    PMID:10399916

    Open questions at the time
    • Whether phosphorylation regulates the rhodopsin–Tctex-1 interaction
    • In vivo validation in photoreceptors not yet shown
  4. 2001 High

    Structural and biochemical studies defined DYNLT1 as a homodimer with an LC8-like fold that binds dynein intermediate chain at a specific 19-residue segment and recognizes cargo via an R/K-rich consensus motif, while parallel work identified CD155 as a second cargo.

    Evidence NMR structure and peptide titration for DIC binding; yeast two-hybrid, co-IP, and mutagenesis for CD155; gel filtration and cross-linking for dimerization

    PMID:11148215 PMID:11278908 PMID:11751937

    Open questions at the time
    • High-resolution structure of the human complex not yet available
    • Whether DIC and cargo binding are mutually exclusive or simultaneous
  5. 2002 High

    DYNLT1 was found to interact with the mitochondrial channel VDAC1 and modulate its electrophysiology, establishing its first non-canonical (non-cargo-adaptor) function.

    Evidence Yeast two-hybrid, overlay assay, immunofluorescence, and planar lipid bilayer electrophysiology

    PMID:12009301

    Open questions at the time
    • Physiological consequence of VDAC1 modulation in cells not established
    • Whether this requires dynein association
  6. 2003 High

    The cargo repertoire expanded to include BMPR-II and PTHR, with BMPR-II shown to phosphorylate DYNLT1 and disease-causing BMPR2 mutations disrupting this interaction, while PTHR binding was required for receptor internalization.

    Evidence Yeast two-hybrid, co-IP, in vitro kinase assay, mutagenesis, and GFP-PTHR internalization assay in MDCK cells

    PMID:14575690 PMID:14583445

    Open questions at the time
    • Identity of the kinase/phosphatase regulating S82 in the PTHR context unknown
    • In vivo role in pulmonary hypertension not directly tested
  7. 2004 High

    DYNLT1 was established as a host factor exploited by viruses for retrograde transport when HSV-1 VP26 was shown to bind Tctex-1 and mediate capsid transport toward the nucleus.

    Evidence Yeast two-hybrid, in vitro pull-down, microinjection of recombinant capsids with live-cell imaging

    PMID:15117959

    Open questions at the time
    • Whether other viral capsid proteins use the same groove
    • Redundancy with other dynein light chains not assessed
  8. 2005 High

    High-resolution structures of Chlamydomonas (NMR) and Drosophila (X-ray) Tctex-1 revealed the domain-swapped homodimeric fold and a target-binding groove analogous to LC8, explaining cargo specificity and the structural basis of dimerization.

    Evidence NMR solution structure and 1.7 Å crystal structure with structural alignment to LC8

    PMID:15698565 PMID:15701632

    Open questions at the time
    • No mammalian apo structure yet
    • How cargo selectivity differs from LC8 at atomic level not fully resolved
  9. 2005 High

    DYNLT1 was shown to selectively interact with N- and P/Q-type voltage-gated Ca²⁺ channels (not L-type) and regulate their surface expression and current density in hippocampal neurons, demonstrating a role in neuronal ion channel trafficking.

    Evidence Co-IP, surface immunostaining, and whole-cell patch-clamp recording in hippocampal neurons

    PMID:15768038

    Open questions at the time
    • Binding site on channel subunit not mapped at residue level
    • Whether phosphorylation at S82 regulates this interaction
  10. 2006 High

    Phosphorylation at S82 was identified as a switch that releases DYNLT1 from the dynein complex while retaining cargo binding; dynamic S82 phosphocycling was shown to be essential for apical rhodopsin delivery in polarized epithelial cells.

    Evidence Phosphomimetic/phospho-dead mutagenesis, velocity sedimentation, and rhodopsin localization in polarized MDCK cells

    PMID:16956385

    Open questions at the time
    • Identity of S82 kinase and phosphatase unknown
    • Whether S82 regulation applies to all cargoes or is rhodopsin-specific
  11. 2007 High

    A dynein-independent function of DYNLT1 was revealed: Gβγ competes with DIC for DYNLT1 binding and the Gβγ-Tctex-1 complex promotes neurite outgrowth through actin/microtubule remodeling, establishing that free (non-dynein-bound) DYNLT1 has signaling roles.

    Evidence Endogenous co-IP from embryonic brain, subcellular fractionation, competitive binding, and functional assays in hippocampal neurons

    PMID:17491591

    Open questions at the time
    • Downstream effectors of the Gβγ-Tctex-1 pathway not identified
    • Whether this pathway operates outside the nervous system
  12. 2009 High

    DYNLT1 was placed upstream of the Rho-GEF Lfc in controlling cortical neurogenesis: Tctex-1 loss promoted neurogenic divisions, and this phenotype was reversed by co-silencing Lfc, demonstrating a dynein-independent role in cell fate determination.

    Evidence shRNA knockdown and epistasis analysis in cortical precursors in culture and in vivo

    PMID:19448628

    Open questions at the time
    • Physical basis for Tctex-1 inhibition of Lfc GEF activity not yet structurally defined
    • Whether this pathway operates in non-neural stem cells
  13. 2011 High

    Phosphorylation at T94 was shown to be the signal for DYNLT1 recruitment to the ciliary transition zone, where it triggers ciliary disassembly and S-phase entry via actin dynamics, establishing DYNLT1 as a cell-cycle gatekeeper at the primary cilium.

    Evidence Phosphomimetic mutagenesis, RNAi, live-cell cilia measurement, and S-phase entry assays in multiple cell types including cortical neural progenitors

    PMID:21394082

    Open questions at the time
    • Identity of T94 kinase unknown at this point
    • Downstream mechanism linking actin to ciliary membrane resorption not defined
  14. 2011 High

    DYNLT1 was identified as a GTP-dependent effector of Rab3D, linking it to secretory vesicle transport in osteoclasts and bone resorption, broadening the cargo adaptor function to small GTPases.

    Evidence Yeast two-hybrid, co-IP with GTP-dependence, RNAi knockdown with bone resorption assay

    PMID:21262767

    Open questions at the time
    • Whether Rab3D and DIC bind simultaneously or competitively
    • Structural basis of GTP-dependent recognition not defined
  15. 2015 Medium

    A dynein-independent kinetochore function was discovered: DYNLT1 localizes to unattached kinetochores via the Ndc80 complex (not the ZW10-dynein pathway) and is required for chromosome alignment and faithful segregation.

    Evidence RNAi knockdown, live-cell imaging, epistasis analysis with Ndc80 and ZW10 components

    PMID:25928583

    Open questions at the time
    • Direct Ndc80–Tctex-1 binding not reconstituted in vitro
    • Whether the kinetochore pool overlaps with the mitotic spindle dynein pool
  16. 2015 High

    NMR mapping showed that RagA GTPase and DIC occupy distinct surfaces on DYNLT1, enabling simultaneous binding and formation of a tripartite DIC–DYNLT1–RagA complex, revealing that cargo binding does not necessarily require release from dynein.

    Evidence NMR chemical shift perturbation, pull-down, mutagenesis

    PMID:26227614

    Open questions at the time
    • Functional consequence of the tripartite complex in mTOR signaling not tested
    • Whether this applies to all cargoes or is RagA-specific
  17. 2016 High

    The first NMR structure of the human DYNLT1–DIC complex was obtained, and pepscan alanine scanning defined the hydrophobic groove residues critical for DIC binding; Lfc and PTHR were shown to use a dual binding mode, and activin receptor IIB was identified as a new ligand.

    Evidence Pepscan substitution analysis, NMR structure of 74 kDa complex, co-IP

    PMID:27502274

    Open questions at the time
    • Structural basis of dual binding mode for Lfc not at atomic resolution
    • Whether activin receptor IIB binding is physiologically relevant in vivo
  18. 2018 High

    DYNLT1 was shown to promote keratinocyte delamination during epidermal stratification by compartmentalizing desmoglein-1-containing desmosomes and enabling cortactin/Arp2/3-dependent perijunctional actin polymerization that reduces E-cadherin tension.

    Evidence Co-IP with Dsg1 and cortactin, RNAi, live-cell imaging, traction force microscopy, stratification assay

    PMID:29535305

    Open questions at the time
    • Whether DYNLT1 acts via dynein or independently in this context
    • Mechanism of Dsg1–Tctex-1 binding not structurally defined
  19. 2023 High

    MAST4 was identified as the kinase responsible for T94 phosphorylation of DYNLT1, resolving the upstream signal for ciliary resorption; MAST4 localizes to the cilium and its activity triggers Cdc42 activation and Rab5-mediated periciliary membrane endocytosis.

    Evidence Kinase assay, co-IP, mutagenesis, RNAi, live-cell ciliary length measurement, Cdc42 activation assay

    PMID:37726137

    Open questions at the time
    • Whether other kinases also phosphorylate T94 in different cell types
    • How pT94-Tctex-1 activates Cdc42 mechanistically
  20. 2023 Medium

    The VDAC1 interaction was mechanistically deepened: DYNLT1 stabilizes VDAC1 on mitochondria by blocking Parkin-mediated ubiquitination and proteasomal degradation, thereby sustaining mitochondrial membrane potential and ATP production in breast cancer cells.

    Evidence Co-IP, ubiquitination assay, immunofluorescence, in vivo xenograft, mitochondrial assays

    PMID:37280526

    Open questions at the time
    • Whether DYNLT1 directly binds Parkin or sterically blocks its access to VDAC1
    • Not replicated by independent groups
    • Relevance beyond breast cancer cells not tested
  21. 2025 Medium

    DYNLT1 knockout in mice produced spontaneous atrial fibrillation with loss of gap junction proteins and ER calcium overload via TMCO1 mislocalization, revealing an in vivo cardiac requirement.

    Evidence CRISPR/Cas9 knockout mouse, ECG, echocardiography, mass spectrometry, co-IP

    PMID:40457945

    Open questions at the time
    • Mechanism connecting DYNLT1 to gap junction protein expression unclear
    • Single study, not independently replicated
    • Whether the cardiac phenotype is cell-autonomous

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: the identity and regulation of the S82 kinase/phosphatase, how phosphorylated DYNLT1 activates Cdc42 at cilia, the structural basis for cargo selectivity across the many known ligands, whether partial DIC occupancy by DYNLT1 (suggested by anti-cooperative binding) has a regulatory role in vivo, and the physiological significance of DYNLT1's dynein-independent functions in tissues beyond the nervous system and epidermis.
  • S82 kinase identity unknown
  • Structural basis for selectivity among dozens of cargoes sharing overlapping binding sites
  • In vivo validation of dynein-independent roles in most tissue contexts

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3
Localization
GO:0005739 mitochondrion 3 GO:0005856 cytoskeleton 3 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005929 cilium 2 GO:0005694 chromosome 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-9612973 Autophagy 1
Partners
ARHGEF2DYNC1I2DYNLL1MAST4NDC80RAB3DRRAGAVDAC1
Complex memberships
cytoplasmic dynein complexflagellar inner dynein arm I1

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Tctex-1 is a stoichiometric 14-kDa light chain subunit of mammalian brain cytoplasmic dynein, co-sedimenting with microtubules in an ATP-dependent manner and co-immunoprecipitated by anti-dynein intermediate chain antibody. Sucrose density gradient sedimentation, microtubule co-sedimentation, co-immunoprecipitation with anti-dynein intermediate chain antibody, peptide sequencing The Journal of biological chemistry High 8943288
1998 Tctex1 is a component of flagellar inner dynein arm I1 (in addition to cytoplasmic dynein), as determined by genetic and biochemical dissection of Chlamydomonas flagella, implicating flagellar dynein dysfunction in t-haplotype meiotic drive. Genetic dissection of Chlamydomonas axonemal mutants, immunoblotting of isolated dynein arms The Journal of cell biology High 9490726
1999 Tctex-1 directly binds the C-terminal cytoplasmic tail of rhodopsin, and cytoplasmic dynein translocates rhodopsin-bearing vesicles along microtubules via this interaction; retinitis pigmentosa-causing C-terminal rhodopsin mutations inhibit this binding. Co-immunoprecipitation, in vitro pull-down, microtubule-based motility assay, yeast two-hybrid, mutagenesis Cell High 10399916
2001 Tctex-1 directly binds the dynein intermediate chain (DIC) at a 19-residue fragment following the second alternative splicing site of DIC; NMR analysis reveals Tctex-1 adopts a fold similar to DLC8 despite no sequence homology, and binds targets via an R/K-R/K-X-X-R/K consensus motif. NMR spectroscopy (backbone NOE, chemical shift), peptide titration, secondary structure determination The Journal of biological chemistry High 11148215
2001 The cytoplasmic domain of poliovirus receptor CD155 binds Tctex-1 via a SKCSR juxtamembrane motif, potentially targeting CD155-containing endocytic vesicles to the microtubule network for retrograde transport. Yeast two-hybrid screen, co-immunoprecipitation, mutagenesis mapping of binding site, immunofluorescence The Journal of biological chemistry High 11751937
2001 Tctex1 forms homodimers in solution (gel filtration, native gel electrophoresis, yeast two-hybrid); Tctex1 and Tctex2 class light chains associate with dynein intermediate chains at the base of the dynein particle and are essential for dynein assembly. Gel filtration chromatography, native gel electrophoresis, yeast two-hybrid, chemical cross-linking, immunoblot The Journal of biological chemistry High 11278908
2002 VDAC1 interacts with Tctex-1 in vivo (yeast two-hybrid, overlay assay with recombinant proteins), co-localizes with Tctex-1 in HeLa cells, and recombinant Tctex-1 modulates the electrophysiological properties of VDAC1 (increases voltage-dependence) in planar lipid bilayer experiments. Yeast two-hybrid (Sos recruitment system), overlay assay, immunofluorescence, planar lipid bilayer electrophysiology The international journal of biochemistry & cell biology High 12009301
2003 BMPR-II cytoplasmic tail interacts with Tctex-1 and phosphorylates Tctex-1; this phosphorylation is disrupted by PPH disease-causing mutations within exon 12 of BMPR2. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, co-localization by immunofluorescence Human molecular genetics High 14583445
2003 Tctex-1 interacts with the COOH-terminal tail of PTH/PTH-related protein receptor (PTHR) via a bipartite motif; mutations in this motif abolish association in vitro, and GFP-fused mutant PTHR impaired in Tctex-1 binding shows decreased internalization in response to PTH. Yeast two-hybrid, in vitro binding assay, site-directed mutagenesis, GFP-PTHR internalization assay in MDCK cells Biochemical and biophysical research communications High 14575690
2004 HSV-1 outer capsid protein VP26 directly binds dynein light chains RP3 and Tctex-1 and is sufficient to mediate retrograde transport of viral capsids; VP26+ capsids co-localize with Tctex-1 and microtubules and move toward the nucleus, while VP26- capsids do not. Yeast two-hybrid, in vitro pull-down with recombinant proteins, microinjection of recombinant capsids into live cells, immunofluorescence co-localization The Journal of biological chemistry High 15117959
2005 NMR solution structure of Chlamydomonas Tctex1 dimer reveals a strand-switched beta-sheet homodimeric interface similar to LC8; structural analysis identifies the dynein intermediate chain binding site and suggests cargo attachment mechanism and basis for cargo specificity relative to rp3. NMR spectroscopy (solution structure), structural comparison Structure High 15698565
2005 Crystal structure of Drosophila TcTex-1 to 1.7 Å reveals a homodimeric domain-swapped fold similar to LC8; the N-terminus binds at the same groove as the nNOS peptide in LC8, indicating TcTex-1 binds targets in an analogous manner. X-ray crystallography (MAD phasing), structural alignment 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 a channel fragment containing the Tctex-1 binding domain decreases surface expression of N- and P/Q-type channels and reduces Ca2+ current density in hippocampal neurons. Co-immunoprecipitation, immunostaining of surface channels, whole-cell Ca2+ current recording in hippocampal neurons Nature neuroscience High 15768038
2006 Phosphorylation of Tctex-1 at serine 82 (S82E phosphomimic) reduces affinity for dynein intermediate chain and prevents incorporation into the dynein complex while retaining rhodopsin binding; both S82E and S82A (dephosphomimic) mutants disrupt apical localization of rhodopsin in polarized MDCK cells, indicating that dynamic phosphorylation-regulated Tctex-1/dynein dissociation is required for apical cargo delivery. Phosphomimetic/phospho-dead mutagenesis, velocity sedimentation, rhodopsin localization in polarized MDCK cells Traffic High 16956385
2006 Tctex-1 dimerization is tightly coupled to folding; equilibrium unfolding follows a two-state model (folded dimer → two unfolded monomers) with no stable monomeric intermediate, unlike the three-state mechanism of structural homolog LC8. Intrinsic fluorescence, fluorescence anisotropy, circular dichroism equilibrium unfolding, sedimentation equilibrium, chemical cross-linking Biochemistry High 16734416
2007 Gβγ binds Tctex-1, forming an endogenous complex in brain; Gβγ co-segregates with dynein-free Tctex-1 fractions and competes with dynein intermediate chain for Tctex-1 binding, regulating Tctex-1 assembly into the dynein motor complex. Tctex-1 and Gβγ promote neurite outgrowth, acting in a dynein-independent pathway modulating actin and microtubule dynamics. Co-immunoprecipitation from embryonic brain extracts, subcellular fractionation, competitive binding assay, dominant-negative and overexpression in hippocampal neurons The EMBO journal High 17491591
2008 Tctex-1 is involved in intracellular targeting of Mason-Pfizer monkey virus (M-PMV) polyproteins to the cytoplasmic assembly site; a single amino acid change (R55F) in M-PMV matrix protein buries the Tctex-1-binding targeting motif, redirecting assembly to the plasma membrane. Biochemical pull-down, 3D structure determination by NMR, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 18647839
2009 Tctex-1 (Dynlt1) negatively regulates Lfc (Arhgef2) activity in cortical precursors; genetic knockdown of Dynlt1 promotes neurogenesis and depletes cycling precursors, while knockdown of Arhgef2 inhibits neurogenesis; co-silencing reverses these effects, placing Tctex-1 upstream of Lfc in controlling neurogenic divisions and mitotic spindle orientation. Genetic knockdown (shRNA) in cortical precursors in culture and in vivo, epistasis analysis by co-silencing Nature neuroscience High 19448628
2010 Tctex-1 co-localizes with and physically interacts with Lfc (a Rho GEF), inhibiting its GEF activity and decreasing Rho-GTP levels, thereby antagonizing Lfc during neurite formation in developing neurons. Co-immunoprecipitation, GEF activity assay (Rho-GTP measurement), co-localization by immunofluorescence, knockdown The Journal of neuroscience High 20463241
2011 Phosphorylated Tctex-1 (pT94) is recruited to ciliary transition zones prior to S-phase entry and is required for ciliary disassembly and cell cycle progression; phosphomimic T94E accelerates cilium disassembly and S-phase entry; this involves actin dynamics; pT94-Tctex-1 is enriched at ciliary transition zones of cortical neural progenitors controlling G1 length and fate determination. Phosphomimetic/phospho-dead mutagenesis, live-cell imaging, RNAi knockdown, S-phase entry assay, primary cilia length measurement, actin perturbation Nature cell biology High 21394082
2011 Tctex-1 binds specifically to Rab3D in a GTP-dependent manner, co-occupies Rab3D-bearing vesicles, and associates with the dynein complex and microtubules in osteoclasts; RNAi knockdown of Tctex-1 impairs bone resorption and mislocalizes Rab3D vesicles. Yeast two-hybrid, co-immunoprecipitation, GTP-dependence assay, immunofluorescence co-localization, RNAi knockdown with bone resorption assay Molecular and cellular biology High 21262767
2011 DYNLT1 interacts with VDAC1 (confirmed by co-immunoprecipitation); DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization, indicating DYNLT1 plays a role in stabilizing mitochondrial permeability under hypoxia. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, siRNA knockdown, mitochondrial permeability assays PloS one Medium 22164227
2011 Flavivirus membrane protein (prM/M) ectodomain interacts with Tctex-1; siRNA silencing of Tctex-1 significantly decreases dengue and West Nile virus progeny production and inhibits production of recombinant dengue subviral particles, placing Tctex-1 in late stages of flavivirus replication. Yeast two-hybrid, GST pull-down, siRNA knockdown with viral titer and subviral particle production assay Virology Medium 21767858
2013 Phosphorylation of DYNLT1 at S82 (phosphomimic S82E) increases free tubulin in cytoplasm, aggravates hypoxia-induced mitochondrial damage (loss of mitochondrial membrane potential, cytochrome c release, mPT pore opening), and decreases cell viability; S82A (dephosphomimic) diminishes hypoxia-induced injury, suggesting S82 phosphorylation regulates microtubule stability and mitochondrial permeability. Phosphomimetic/phospho-dead adenoviral constructs, mitochondrial membrane potential assay, cytochrome c release, mPT pore opening assay, ATP quantification, tubulin fractionation Molecules and cells Medium 24170091
2015 Chlamydia trachomatis inclusion membrane protein CT850 interacts with DYNLT1 via an R/K-R/K-X-X-R/K motif; DYNLT1 is enriched at focal CT850 concentrations on the inclusion membrane, and DYNLT1 depletion disrupts inclusion-centrosome association. Yeast two-hybrid, ectopic expression localization assay, siRNA knockdown with centrosome association assay Biochemical and biophysical research communications Medium 25944661
2015 Tctex-1 associates with unattached kinetochores independently of its dynein association; Tctex-1 knockdown produces mitotic arrest with misaligned chromosomes that are subsequently missegregated; kinetochore localization requires the Ndc80 complex but not the ZW10-dynein pathway. RNAi knockdown, immunofluorescence, live-cell imaging, epistasis analysis with Ndc80 and ZW10 pathway components Cell cycle Medium 25928583
2015 DYNLT forms a tripartite complex with dynein intermediate chain and RagA GTPase; NMR identifies distinct residues of DYNLT affected by DIC binding versus RagA binding; both microtubule-associated and cytoplasmic DYNLT can bind Rab3D and RagA. NMR spectroscopy, pulldown assays, mutagenesis The FEBS journal High 26227614
2016 The hydrophobic groove of DYNLT1 that accommodates dynein intermediate chain was characterized by pepscan alanine scanning; activin receptor IIB was identified as a novel DYNLT1 ligand; NMR solution structure of human DYNLT1 complexed with dynein IC (~74 kDa) was obtained, the first mammalian DYNLT1 structure; Lfc and PTHR use a dual binding mode to DYNLT1. Pepscan substitution analysis, NMR spectroscopy (complex structure), co-immunoprecipitation 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 reducing tension at E-cadherin junctions to promote keratinocyte delamination during epidermal stratification. Co-immunoprecipitation, RNAi knockdown, live-cell imaging, traction force microscopy, stratification assay Nature communications High 29535305
2018 Tctex-1 associates with KIM-1 at baseline in cells but dissociates within 90 min of efferocytosis initiation; KIM-1 expression inhibits phosphorylation of Tctex-1 at T94, maintaining Tctex-1 in its dynein-bound form; shRNA silencing of Tctex-1 significantly inhibits KIM-1-dependent efferocytosis. Yeast two-hybrid, co-immunoprecipitation, confocal imaging, shRNA knockdown with efferocytosis assay, phosphorylation analysis Journal of cellular physiology Medium 29693725
2020 miR-15b-3p directly targets DYNLT1 (validated by dual-luciferase reporter assay); suppression of DYNLT1 by exosomal miR-15b-3p reduces Cleaved Caspase-9 and Caspase-3, promoting gastric cancer cell survival and malignant transformation. Dual-luciferase reporter assay, Western blotting, qRT-PCR, xenograft models, exosome transfer assay Journal of experimental & clinical cancer research Medium 32039741
2020 Tctex-1 augments PTH receptor-mediated Gs/adenylyl cyclase signaling by directly binding and activating adenylyl cyclase type 6, independently of its binding to PTHR. cAMP assay, co-immunoprecipitation of Tctex-1 with adenylyl cyclase type 6, overexpression/knockdown in cells 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 in breast cancer cells. Co-immunoprecipitation, ubiquitination assay, immunofluorescence co-localization, in vivo xenograft, mitochondrial membrane potential and ATP assays 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 knockdown blocks serum-induced ciliary resorption and ciliary base localization of pT94-Tctex-1, and MAST4 catalytic-inactive mutants phenocopy this; MAST4-mediated ciliary resorption involves Cdc42 activation and Rab5-mediated periciliary membrane endocytosis. Kinase assay, co-immunoprecipitation, site-directed mutagenesis, RNAi knockdown, live-cell ciliary length measurement, Cdc42 activation assay Life science alliance High 37726137
2025 DYNLT1 knockout in mice (CRISPR/Cas9) induces spontaneous atrial fibrillation associated with downregulation of gap junction proteins, increased cardiomyocyte apoptosis, and reduced distribution of TMCO1 in the ER of atrial cardiomyocytes, leading to ER calcium overload. CRISPR/Cas9 knockout, ECG, echocardiography, histology, mass spectrometry, immunofluorescence, co-IP Biology open Medium 40457945
2025 Thermodynamic analysis of IC/LC8/Tctex1 binding reveals anti-cooperativity between LC8 and Tctex1 binding to the dynein intermediate chain; Tctex1 binding exhibits negative cooperativity (second binding weaker than first), distinct from LC8's positive cooperativity; the half-bound IC state is prevalent, suggesting a functional role for partial occupancy. Isothermal titration calorimetry (39 isotherms), Bayesian inference thermodynamic modeling 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 412 10399916
2011 Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nature cell biology 192 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 131 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 74 19448628
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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 51 29535305
2015 Chlamydia trachomatis inclusion membrane protein CT850 interacts with the dynein light chain DYNLT1 (Tctex1). Biochemical and biophysical research communications 47 25944661
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2006 Regulatory dissociation of Tctex-1 light chain from dynein complex is essential for the apical delivery of rhodopsin. Traffic (Copenhagen, Denmark) 34 16956385
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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
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