Affinage

DYNC1LI2

Cytoplasmic dynein 1 light intermediate chain 2 · UniProt O43237

Length
492 aa
Mass
54.1 kDa
Annotated
2026-06-09
13 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DYNC1LI2 (LIC2) is a light intermediate chain of cytoplasmic dynein-1 that defines a functionally distinct motor complex from its paralog LIC1, specializing in endomembrane positioning and trafficking (PMID:19386764, PMID:21169557). Depletion of LIC2, but not LIC1, perturbs recycling endosome distribution and cytokinesis, and disrupts late endosome and lysosome positioning, establishing non-redundant roles for the two LIC-containing dyneins (PMID:19386764, PMID:21169557). LIC2 is recruited onto membranes through cargo-specific adaptors: Rab11-FIP3 bridges Rab11a to LIC2 to drive accumulation of recycling cargo at the pericentrosomal endosomal-recycling compartment (PMID:20214888), while KASH5 engages a conserved C-terminal helix of the LIC to act as an activating adaptor for dynein motility during meiotic chromosome movement, with this same region serving more broadly in dynein recruitment to membranes (PMID:36946995). Beyond trafficking, LIC2 regulates localization of the chaperone-mediated autophagy receptor LAMP2A and supports CMA activity, endolysosomal dynamics, and stress resistance in a RAB7/RAB11- and LAMP2A-dependent, paralog-specific manner (PMID:34643468). LIC2 is post-translationally regulated by PRMT1-mediated methylation at arginine 397, a modification absent from LIC1 (PMID:38525916).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2009 High

    Established that LIC2 is not redundant with LIC1 but defines a distinct dynein complex acting at recycling endosomes and in cytokinesis, answering whether the two LIC paralogs are functionally interchangeable.

    Evidence Reciprocal RNAi knockdown of LIC1 and LIC2 with automated phenotypic image analysis in mammalian cells

    PMID:19386764

    Open questions at the time
    • Did not identify the membrane adaptor linking LIC2 to recycling endosomes
    • No structural basis for paralog-specific cargo selectivity
  2. 2010 High

    Extended LIC2 function to the late endocytic pathway, showing LIC2 controls lysosome and late endosome distribution alongside LIC1 at these compartments.

    Evidence RNAi, isoform-specific antibody localization, subcellular fractionation, and RILP-stimulated transport assay

    PMID:21169557

    Open questions at the time
    • Mechanism distinguishing LIC1 vs LIC2 contributions at late endosomes not resolved
    • Adaptor for late-endosome recruitment not defined
  3. 2010 Medium

    Identified Rab11-FIP3 as the adaptor coupling Rab11a-positive membranes to LIC2, explaining how LIC2 is recruited to drive recycling-compartment cargo accumulation.

    Evidence Co-immunoprecipitation, pulldown domain mapping (FIP3 N-terminal 435 aa), and transferrin endocytosis assay

    PMID:20214888

    Open questions at the time
    • Single lab, no in vitro reconstitution of the FIP3-LIC2-dynein complex
    • Binding region on LIC2 not mapped
  4. 2011 Medium

    Distinguished mitotic localizations of the two LIC complexes, placing LIC2 at spindle poles and LIC1 at spindle/midbody, implying separate mitotic roles.

    Evidence Immunofluorescence at multiple mitotic stages in dividing cells

    PMID:20964624

    Open questions at the time
    • No functional perturbation of LIC2 at spindle poles
    • Mechanism of pole-specific targeting unknown
  5. 2021 High

    Connected LIC2 to chaperone-mediated autophagy by showing it governs LAMP2A localization and CMA activity, with reconstitution rescuing endolysosomal, ER-stress, and mitochondrial defects in disease-model cells.

    Evidence Reconstitution in ctns-/- cells, dominant-negative RAB7/RAB11, LAMP2A knockdown, CMA assay, mitochondrial imaging

    PMID:34643468

    Open questions at the time
    • Direct LIC2-LAMP2A physical link not established
    • How RAB7/RAB11 dependence is integrated mechanistically unresolved
  6. 2023 High

    Defined the LIC C-terminal helix as the binding site for the activating adaptor KASH5 and showed this region also mediates dynein recruitment to other membranes, providing a structural mechanism for LIC2-based motor activation.

    Evidence In vitro dynein motility reconstitution, domain mapping, KASH5 EF-hand mutagenesis, and Co-IP

    PMID:36946995

    Open questions at the time
    • Does not separate LIC1- vs LIC2-specific contributions to KASH5 binding
    • Regulation of the helix interaction in somatic membrane recruitment unclear
  7. 2024 Medium

    Revealed a paralog-specific regulatory layer by identifying PRMT1-mediated arginine-397 methylation on LIC2 but not LIC1.

    Evidence Immunoprecipitation, immunoblotting, site-directed mutagenesis, bioinformatics

    PMID:38525916

    Open questions at the time
    • Functional consequence of R397 methylation not demonstrated
    • Single lab, no in vivo validation
  8. 2025 Medium

    Implicated locally translated Dync1li2 mRNA in radial glial endfeet for basal morphology and cortical interneuron organization, extending LIC2 function to compartment-specific roles in development.

    Evidence In vivo CRISPR-Cas13 compartment-specific knockdown, RGC compartment purification, subcellular transcriptome analysis (preprint)

    PMID:41280023

    Open questions at the time
    • Preprint, not peer-reviewed
    • Link between local translation and dynein motor function not mechanistically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and regulatory logic that makes LIC2 cargo- and process-selective relative to LIC1 remains incompletely defined.
  • No structure of LIC2-containing dynein with paralog-specific adaptors
  • Functional output of PRMT1 methylation unknown
  • How a single LIC2 subunit coordinates recycling, CMA, and mitotic roles is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0008092 cytoskeletal protein binding 1 GO:0140657 ATP-dependent activity 1
Localization
GO:0005768 endosome 3 GO:0005764 lysosome 2 GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 1
Partners
KASH5LAMP2ALIS1PRMT1RAB11FIP3
Complex memberships
cytoplasmic dynein-1

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 DYNC1LI2 (LIC2) depletion by RNAi causes defects in recycling endosome distribution and cytokinesis, while depletion of DYNC1LI1 (LIC1) does not, demonstrating that LIC2 defines a distinct dynein complex functioning at recycling endosomes versus the LIC1-containing complex at the Golgi. RNAi knockdown with automated image analysis in mammalian cells Molecular biology of the cell High 19386764
2010 DYNC1LI2 (LIC2) RNAi disrupts the distribution of lysosomes and late endosomes; LIC1 and LIC2 are both specifically associated with elements of the late endocytic pathway but not other vesicular compartments, as revealed by isoform-specific antibodies and subcellular fractionation. RNAi knockdown, isoform-specific antibodies, subcellular localization, RILP-stimulated transport assay Molecular biology of the cell High 21169557
2010 Rab11-FIP3 binds DYNC1LI2 via the amino-terminal 435 amino acids of FIP3, links Rab11a to DYNC1LI2, recruits DYNC1LI2 onto membranes, and DYNC1LI2 is required for accumulation of endocytosed transferrin at the pericentrosomal endosomal-recycling compartment (ERC). Co-immunoprecipitation, pulldown, overexpression, endocytosis assay in mammalian cells Biochemical and biophysical research communications Medium 20214888
2011 DYNC1LI2 (LIC2) localizes to spindle poles from prophase through telophase during cell division, while LIC1 localizes to the mitotic spindle and midbody, indicating distinct mitotic roles for LIC1- and LIC2-containing dynein complexes. Immunofluorescence localization in dividing cells Cell biology international Medium 20964624
2021 DYNC1LI2 regulates the localization of the chaperone-mediated autophagy (CMA) receptor LAMP2A and CMA activity; reconstitution of DYNC1LI2 in cystinotic (ctns−/−) cells restores endolysosomal dynamics, reduces ER stress, rescues mitochondrial fragmentation, and improves cell survival to oxidative stress. These effects depend on RAB7 and RAB11 activity and LAMP2A, and are not replicated by the paralog DYNC1LI1. mRNA/protein expression analysis, reconstitution in ctns−/− cells, dominant-negative RAB7/RAB11 expression, LAMP2A knockdown, CMA activity assay, mitochondrial imaging Autophagy High 34643468
2023 KASH5 interacts with DYNC1LI2 (or DYNC1LI1) through a conserved helix in the LIC C-terminal region to act as an activating adaptor for cytoplasmic dynein during meiotic chromosome movement; this region is also required for dynein recruitment to other cellular membranes. LIS1 is essential for dynactin incorporation into the KASH5-dynein complex. In vitro dynein motility assay, binding domain mapping, mutagenesis of KASH5 EF-hands, co-immunoprecipitation, cell biology assays The Journal of cell biology High 36946995
2024 DYNC1LI2 is specifically methylated at arginine residue 397 by protein arginine methyltransferase 1 (PRMT1), a post-translational modification not found on the paralog DYNC1LI1, identifying a regulatory mechanism specific to LIC2-containing dynein complexes. Immunoprecipitation, immunoblotting, site-directed mutagenesis, bioinformatics Journal of clinical laboratory analysis Medium 38525916
2025 Endfoot-localized Dync1li2 mRNA in radial glial cells (RGCs) is critical for RGC basal morphology and interneuron organization; subcellular (endfoot-specific) knockdown of Dync1li2 using CRISPR-Cas13 disrupts RGC basal morphology, demonstrating a compartment-specific function of locally translated DYNC1LI2 in cortical development. In vivo compartment-specific RNAi (CRISPR-Cas13 LOCAL-KD), RGC compartment purification, subcellular transcriptome analysis bioRxivpreprint Medium 41280023

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Specificity of cytoplasmic dynein subunits in discrete membrane-trafficking steps. Molecular biology of the cell 101 19386764
2010 Recruitment of dynein to late endosomes and lysosomes through light intermediate chains. Molecular biology of the cell 71 21169557
2010 Rab11-FIP3 binds dynein light intermediate chain 2 and its overexpression fragments the Golgi complex. Biochemical and biophysical research communications 56 20214888
2008 A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23. Neurology 43 18463364
2013 Dysferlin interacts with calsequestrin-1, myomesin-2 and dynein in human skeletal muscle. The international journal of biochemistry & cell biology 27 23792176
2023 The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein. The Journal of cell biology 20 36946995
2011 Dynein LIC1 localizes to the mitotic spindle and midbody and LIC2 localizes to spindle poles during cell division. Cell biology international 18 20964624
2021 DYNC1LI2 regulates localization of the chaperone-mediated autophagy receptor LAMP2A and improves cellular homeostasis in cystinosis. Autophagy 14 34643468
2021 The expression, localisation and interactome of pigeon CRY2. Scientific reports 9 34645873
2025 Subcellular transcriptome of radial glia reveals compartmentalized control of cortical development. bioRxiv : the preprint server for biology 2 41280023
2022 Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer. Frontiers in cell and developmental biology 1 35265610
2025 Impact of copper nanoparticles (CuNPs) on gonadal development in zebrafish larvae and melatonin therapeutic intervention. Aquatic toxicology (Amsterdam, Netherlands) 0 40683198
2024 Dynein Light Intermediate Chains Exhibit Different Arginine Methylation Patterns. Journal of clinical laboratory analysis 0 38525916

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