| 2011 |
DYNLL1 and DYNLL2 (LC8 family) function as regulatory hub proteins that interact with short linear motifs (KXTQT and XG(I/V)QVD) in intrinsically disordered segments of binding partners, promoting dimerization of those partners rather than acting as simple cargo adaptors for dynein/myosin motors. Binding partners include the dynein intermediate chain, myosin 5a, and diverse scaffold proteins. |
Review synthesizing structural and functional studies; yeast two-hybrid, peptide binding, co-IP, structural data from multiple labs |
The FEBS journal |
High |
21777386
|
| 2010 |
DYNLL2 binds two putative consensus motifs (KXTQTX and XG(I/V)QVD) with micromolar affinity, with the KXTQTX motif showing slower off-rate constants. Binding kinetics best fit a conformational selection model (slow isomerization + rapid binding). A phosphomimetic S88E mutant of DYNLL2 shows significantly lower apparent Kd for dimeric myosin Va, suggesting phosphorylation modulates binding affinity. Bivalent (dimeric) ligands show strong avidity effects (nanomolar Kd). |
In vitro binding assays (isothermal titration calorimetry, surface plasmon resonance), site-directed mutagenesis of DYNLL2 (S88E), comparison of both DYNLL1 and DYNLL2 isoforms |
The Journal of biological chemistry |
High |
20889982
|
| 2014 |
DYNLL2 binds to an extended linear motif in the intrinsically disordered tail of myosin 5a. In the free form the motif has nascent helical character; upon DYNLL2 binding it folds into a β-strand occupying each of the two parallel binding grooves of the DYNLL2 homodimer. Flanking residues make additional contacts: the N-terminal extension folds back to partially block the free β-sheet edge, and the C-terminal extension contacts the dimer interface and interacts with the symmetry-related second myosin 5a peptide. |
NMR spectroscopy, X-ray crystallography, molecular dynamics simulations |
Biochemistry |
High |
25312846
|
| 2014 |
DYNLL1 and DYNLL2 are subunits of the human cytoplasmic dynein-2 complex, which mediates retrograde intraflagellar transport (IFT). They associate with the dynein-2 intermediate chain WDR34. The dynein-2 complex composition was defined to include DYNLL1/DYNLL2 as shared subunits. |
Co-immunoprecipitation/mass spectrometry to define complex composition; siRNA knockdown functional assays for cilia |
Journal of cell science |
High |
25205765
|
| 2014 |
DYNLL1 and DYNLL2 localize to cilia in puncta consistent with IFT particles and physically interact with WDR34, a dynein-2 intermediate chain. Expression of DYNLL2 (as well as DYNLL1) rescued ciliogenesis defects caused by ATMIN/DYNLL1 depletion, placing DYNLL2 downstream of ATMIN in ciliogenesis. |
Immunofluorescence localization to cilia, co-immunoprecipitation with WDR34, rescue experiments by exogenous DYNLL2 expression in ATMIN-depleted cells |
Development (Cambridge, England) |
Medium |
25294941
|
| 2018 |
DYNLL1 and DYNLL2 associate with the WDR34 intermediate chain subcomplex of dynein-2 (WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2). This subcomplex is one of three defined subcomplexes in dynein-2. |
Visible immunoprecipitation (VIP) assay mapping pairwise and higher-order interactions among dynein-2 subunits |
Molecular biology of the cell |
Medium |
29742051
|
| 2019 |
The WDR34 intermediate chain interacts with DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2 via distinct sites. These interactions are required for retrograde ciliary protein trafficking; WDR34 constructs lacking the DYNLL-binding N-terminal region act in a dominant-negative manner, inhibiting ciliary biogenesis and retrograde trafficking. |
Co-immunoprecipitation, knockout cell lines expressing WDR34 deletion/mutant constructs, dominant-negative analysis, ciliary trafficking assays |
Molecular biology of the cell |
High |
30649997
|
| 2012 |
DYNLL2 (DLC2) interacts with the postsynaptic scaffold protein GKAP in dendritic spines. This interaction stabilizes scaffolding protein expression at the postsynaptic density and enhances synaptic NMDA receptor activity. The interaction is favored by sustained synaptic activity. |
BRET imaging, immunostaining, electrophysiological recording of NMDA receptor-mediated currents, co-expression of interaction-deficient mutants |
Journal of cell science |
Medium |
22328512
|
| 2014 |
DYNLL2 (DLC2) dimerization is required for its interaction with GKAP. DLC2-GKAP hetero-oligomeric complexes in dendritic shafts comprise ~2 DLC2 and ~2 GKAP monomers, while in dendritic spines the complexes are much larger (~16 DLC2 and ~13 GKAP monomers). Disruption of the GKAP-DLC2 interaction destabilizes these oligomers, decreases spine-preferential localization of GKAP, and inhibits NMDA receptor activity. DLC2 thus acts as a dimerization engine for GKAP to organize the postsynaptic scaffold. |
Two-photon scanning number and brightness (sN&B) fluorescence fluctuation microscopy in living neurons, GKAP-DLC2 interaction-deficient mutants |
Journal of cell science |
High |
24938595
|
| 2019 |
DYNLL1 and DYNLL2 both interact with the BH3-only proteins Bim and Bmf (not exclusively isoform-specific). DYNLL1/2 induces homodimerization of Bim and Bmf and promotes formation of ternary Bim-DYNLL-Bmf complexes in cell-free and cellular systems. DYNLL-induced oligomerization stabilizes Bmf by inhibiting its degradation by the ubiquitin-independent 20S proteasome. A DYNLL-binding-deficient Bmf mutant fails to induce Bim degradation upon overexpression, demonstrating that Bmf-induced Bim degradation is mediated through modulation of Bim-DYNLL association rather than displacement from anti-apoptotic Bcl-2 proteins. |
Co-immunoprecipitation in cell-free and cellular systems, proteasome degradation assays, overexpression of DYNLL-binding-deficient mutants, cell death assays |
Cell death and differentiation |
High |
31189926
|
| 2011 |
DYNLL1 (but not DYNLL2) is expressed in retinal ganglion cells (RGCs), while DYNLL2 is expressed in glia. DYNLL1 is persistently downregulated in glaucomatous RGCs at all measured timepoints. DYNLL2 is upregulated in glia at 2 weeks after glaucoma induction. These findings indicate non-redundant, cell-type-specific expression patterns for the two isoforms in the retina. |
Laser capture microdissection of RGCs and GCL, quantitative PCR, immunostaining, rat chronic glaucoma model |
Experimental eye research |
Medium |
21145319
|
| 2023 |
DYNLL2 interacts with MBNL1 in an RNA-independent manner. In neurons, overexpressed MBNL1 and DYNLL2 co-traffic along axonal processes. MBNL1 knockdown impairs retrograde movement of DYNLL2, and in DM1 model brains with reduced cytoplasmic MBNL1, DYNLL2 and activated pTrkB accumulate in the synaptosomal fraction, indicating impaired DYNLL2-dependent retrograde transport of the BDNF-TrkB signaling complex. |
Co-immunoprecipitation (RNA-independent), time-lapse live imaging of MBNL1 and DYNLL2 co-movement, shRNA knockdown, subcellular fractionation, DM1 mouse model and postmortem human tissue analysis |
Acta neuropathologica communications |
Medium |
36922901
|
| 2025 |
DYNLL2 interacts with PAK1 to regulate endocytosis of Gram-negative bacterial outer membrane vesicles (OMVs), facilitating cytosolic LPS release and subsequent Caspase-11 inflammasome activation, thereby triggering pyroptosis (GSDMD cleavage). Depletion of DYNLL2 suppresses OMV internalization, Caspase-11/GSDMD cleavage, and proinflammatory cytokine release. Oroxylin A was identified as an inhibitor of the DYNLL2-PAK1 interaction, blocking Caspase-11-dependent pyroptosis in vitro and improving survival in murine endotoxemia models. |
Co-immunoprecipitation (DYNLL2-PAK1 interaction), siRNA/shRNA knockdown of DYNLL2 and PAK1, OMV internalization assays, caspase-11/GSDMD cleavage assays, virtual screening, in vitro pharmacological inhibition, murine endotoxemia model |
Biochemical pharmacology |
Medium |
41360226
|
| 2015 |
DYNLL2 levels are regulated by fed/fasted states in oxytocin neurons of the hypothalamic paraventricular nucleus, with higher DYNLL2 expression under fed conditions correlating with increased NMDA receptor-mediated excitatory postsynaptic currents, suggesting DYNLL2 participates in NMDA receptor trafficking to the postsynaptic site under metabolic regulation. |
Electrophysiological recording (mEPSC and NMDA-EPSCs), western blot/immunostaining for DYNLL2 in PVN oxytocin neurons, fed vs. fasted paradigm |
Neuropeptides |
Low |
26344333
|
| 2011 |
DYNLL1 binds to multiple SQ/TQ motifs in the C-terminal domain of ATMIN via KXTQT-type linear motifs. Co-expression of mCherry-DYNLL1 and GFP-ATMIN mutually affects intracellular localization: DYNLL1 presence partly impedes DNA-damage-induced nuclear foci formation by ATMIN. (Note: DYNLL2 is implied to share similar binding capacity but DYNLL1 was the primary focus.) |
Yeast two-hybrid screen, pepscan, recombinant expression/gel filtration, NMR-modeled complexes, co-expression fluorescence localization, DNA damage assay |
Biochemical and biophysical research communications |
Medium |
21971545
|