Affinage

CHODL

Chondrolectin · UniProt Q9H9P2

Length
273 aa
Mass
30.4 kDa
Annotated
2026-06-09
25 papers in source corpus 13 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHODL (chondrolectin) is a type I transmembrane C-type lectin that operates at the interface of cell-surface glycan recognition and tissue morphogenesis, with established roles in motor neuron axon guidance, skeletal muscle satellite cell maintenance, and a distinct cortical GABAergic neuron identity (PMID:12079284, PMID:22457492, PMID:42088368, PMID:40964242). The protein carries a single extracellular C-type lectin carbohydrate recognition domain, is N-glycosylated, and localizes to the ER-Golgi compartment, where it colocalizes with the ER-Golgi marker rBet1; its short cytoplasmic domain directly binds Rabggtb, the beta-subunit of Rab geranylgeranyl transferase (PMID:12079284, PMID:12621022, PMID:18161010). Alternatively spliced soluble isoforms that lack the transmembrane domain and terminate in a QDEL ER-retention signal are expressed selectively in maturing T lymphocytes and reside in the late endoplasmic reticulum (PMID:12621022, PMID:17606388). In motor neurons, correct CHODL dosage is required for growth cone interactions with intermediate targets: zebrafish chodl knockdown stalls motor axons at the horizontal myoseptum and reduces muscle innervation, a defect rescued by re-expression, and Chodl is aberrantly spliced in SMA spinal motor neurons where restoring its expression rescues outgrowth in Smn-depleted zebrafish (PMID:22457492, PMID:24067532). In skeletal muscle, CHODL is dispensable for development but essential for regeneration, maintaining satellite cell self-renewal, proliferation, sublaminar niche localization within the basal lamina, and Notch signaling (PMID:42088368, PMID:40964242). CHODL also marks a population of long-range somatostatin GABAergic neurons (Sst-Chodl) whose activity drives cortical synchrony and sleep [PMID:bio_10.1101_2024.06.20.599756, PMID:40997796].

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 Medium

    Established the basic identity of CHODL as a type I transmembrane C-type lectin, defining its domain architecture and subcellular distribution and excluding hyaluronan as a ligand.

    Evidence PCR cloning, Western blot, immunohistochemistry, and transfection/localization imaging in COS1 cells

    PMID:12079284

    Open questions at the time
    • No physiological glycan ligand identified for the CRD
    • Functional consequence of perinuclear localization unresolved
  2. 2003 Medium

    Defined the ER-Golgi localization of the transmembrane isoform and discovered a soluble, transmembrane-lacking splice variant expressed selectively in T lymphocytes, indicating isoform-specific deployment.

    Evidence RT-PCR splicing analysis and double-label immunofluorescence with the ER-Golgi marker rBet1; in situ hybridization and immunostaining of mouse muscle

    PMID:12621022 PMID:12711387

    Open questions at the time
    • Function of the soluble T-cell isoform not determined
    • Why a secretory-pathway lectin localizes to ER-Golgi rather than the surface is unexplained
  3. 2007 Low

    Refined the soluble isoform's localization to the late ER via a QDEL retention signal and mapped its expression to discrete lymphocyte subpopulations.

    Evidence Immunofluorescence and immunohistochemistry on spleen, tonsil, and thymocyte tissue

    PMID:17606388

    Open questions at the time
    • Single primary method without functional readout
    • No link between ER retention and any lymphocyte function
  4. 2008 Medium

    Identified the first physical partner of CHODL, showing its cytoplasmic tail binds the beta-subunit of Rab geranylgeranyl transferase, hinting at a link to Rab-dependent membrane trafficking.

    Evidence SOS recruitment yeast screen with in vitro pulldown and co-immunoprecipitation confirmation

    PMID:18161010

    Open questions at the time
    • Functional consequence of the Rabggtb interaction not tested
    • Single lab; reciprocal in vivo validation absent
  5. 2012 High

    Demonstrated a dosage-sensitive requirement for CHODL in motor axon pathfinding, establishing its role in growth cone interactions with intermediate targets.

    Evidence Morpholino knockdown, overexpression, and rescue with live imaging of motor axons in zebrafish

    PMID:22457492

    Open questions at the time
    • Molecular ligand at the horizontal myoseptum not identified
    • Whether the CRD mediates the guidance interaction is untested
  6. 2013 High

    Connected CHODL dysregulation to disease by showing its aberrant splicing in SMA motor neurons and that restoring its expression rescues outgrowth defects in an Smn-deficient model.

    Evidence Exon-level splicing analysis in SMA mice, in vitro neurite/survival assays, and overexpression rescue in smn-knockdown zebrafish

    PMID:24067532

    Open questions at the time
    • Mechanism by which SMN controls Chodl splicing not defined
    • Whether Chodl correction is therapeutic in mammalian SMA untested
  7. 2011 Medium

    Implicated CHODL in cell growth and invasion, suggesting its morphogenetic activity can be co-opted in cancer.

    Evidence siRNA knockdown viability assays, overexpression, and Matrigel invasion assay in lung cancer cells

    PMID:22016508

    Open questions at the time
    • Signaling pathway driving invasion not defined
    • No in vivo tumor model
  8. 2019 Low

    Flagged CHODL as a candidate S-palmitoylation substrate at a juxtamembrane cysteine, a potential layer of post-translational regulation.

    Evidence Machine-learning topology prediction (TopoPalmTree) with brief experimental assessment in the mouse transmembrane proteome

    PMID:39909380

    Open questions at the time
    • Primarily computational; experimental confirmation reported without full detail
    • Functional role of palmitoylation unknown
  9. 2025 Medium

    Established CHODL as a marker of a functionally distinct cortical neuron class, with Sst-Chodl GABAergic cells driving cortical synchrony and sleep through long-range projections.

    Evidence In vivo electrophysiology/calcium imaging and optogenetic activation with behavioral sleep assays in mice (preprint)

    PMID:bio_10.1101_2024.06.20.599756

    Open questions at the time
    • Whether CHODL protein itself contributes to the neuron's function vs. being a marker is untested
    • Preprint, single lab
  10. 2025 Medium

    Linked the Sst_Chodl neuron subtype to sleep disturbance in a 15q13.3 microdeletion disease model, where its hyperactivity is causally responsible and chemogenetic silencing is rescuing.

    Evidence snRNA-seq, patch-clamp, calcium imaging, and chemogenetic inhibition with behavioral rescue in mutant mice

    PMID:40997796

    Open questions at the time
    • Role of CHODL gene product in the phenotype not dissected
    • Mechanism of subtype-selective vulnerability unknown
  11. 2025 High

    Defined a non-redundant requirement for CHODL in adult muscle regeneration, controlling satellite cell self-renewal, niche localization, and Notch signaling without affecting development.

    Evidence Conditional Cre-lox knockout in embryonic myoblasts and adult satellite cells, scRNA-seq, regeneration assays, and localization immunofluorescence

    PMID:40964242 PMID:42088368

    Open questions at the time
    • Direct ECM ligand engaged by the CRD in the niche not identified
    • How CHODL mechanistically links to Notch signaling unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical activity of the CHODL lectin domain remains undefined: no physiological carbohydrate ligand is known, and it is unclear whether its varied tissue roles share a common molecular mechanism.
  • No identified glycan/protein ligand for the CRD
  • No unifying biochemical mechanism across neurons, muscle, and cancer
  • Role of the Rabggtb interaction in any tissue phenotype untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2
Partners

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CHODL encodes a type I transmembrane protein with a single C-type lectin carbohydrate recognition domain (CRD) in its extracellular portion; it is N-glycosylated (~36 kDa) and shows predominantly perinuclear localization in transiently transfected COS1 cells; no specific interaction with hyaluronan was detected. PCR cloning, Northern blot, RT-PCR, immunohistochemistry, Western blot, transient transfection with subcellular localization imaging, cetylpyridinium chloride precipitation (negative for hyaluronan binding) Genomics Medium 12079284
2003 An alternatively spliced CHODL isoform lacking the transmembrane domain (CHODLfΔE/CHODLΔe) is expressed exclusively in T lymphocytes and is regulated during T lymphopoiesis; the transmembrane-containing isoform CHODLf colocalizes with rBet1 to the endoplasmic reticulum–Golgi apparatus. RT-PCR, database analysis, double-label immunofluorescence The Journal of biological chemistry Medium 12621022
2003 Mouse Chodl (orthologue of human CHODL) is a type I transmembrane C-type lectin expressed in skeletal muscle cells during both proliferation and differentiation phases, as shown by in situ hybridization on E15 embryos and fluorescent immunostaining localizing the protein to striated muscle cells. RT-PCR/Southern blotting, in situ hybridization, fluorescent immunostaining, Western blot on C2C12 myoblasts Gene Medium 12711387
2007 The soluble CHODL isoforms (CHODLΔe/CHODLfΔe), which lack the transmembrane domain and terminate in a QDEL ER-retention signal, localize to the late endoplasmic reticulum and are expressed in a small lymphocyte population in spleen and tonsils, with differential expression in thymocytes versus peripheral lymphocytes. Immunofluorescence localization, immunohistochemistry on tissue sections Cell biology international Low 17606388
2008 The cytoplasmic domain of mouse chondrolectin (chodl) directly interacts with the beta-subunit of Rab geranylgeranyl transferase (Rabggtb), identified by SOS recruitment system (SRS) yeast screen and confirmed by in vitro transcription/translation and co-immunoprecipitation. SOS recruitment system (SRS) yeast two-hybrid screen, in vitro transcription/translation pulldown, co-immunoprecipitation Cellular & molecular biology letters Medium 18161010
2012 In zebrafish, knockdown of chodl causes arrest/stalling of motor axon growth at the horizontal myoseptum (an intermediate target), resulting in reduced muscle innervation; this phenotype is rescued by chodl overexpression, demonstrating that correct chodl expression levels are required for growth cone interactions with the horizontal myoseptum. In vivo morpholino knockdown, transgenic overexpression, rescue experiment, in vivo live imaging of labeled motor axons in zebrafish The Journal of neuroscience High 22457492
2013 Chodl expression is altered (alternatively spliced) in SMA mouse spinal motor neurons before symptom onset; in vitro studies show Chodl affects cell survival and neurite outgrowth; increasing chodl expression in Smn-depleted zebrafish rescues motor neuron outgrowth defects, linking Chodl dysregulation to SMA motor neuron pathophysiology. Exon-level splicing analysis in SMA mouse model, in vitro cell survival and neurite outgrowth assays, in vivo chodl overexpression rescue in smn-knockdown zebrafish Human molecular genetics High 24067532
2011 siRNA-mediated knockdown of CHODL suppresses lung cancer cell growth, and exogenous overexpression of CHODL confers growth and invasive activity in mammalian cells, as measured by Matrigel invasion assays. siRNA knockdown (cell viability assay), exogenous CHODL overexpression, Matrigel invasion assay Clinical cancer research Medium 22016508
2019 CHODL is predicted to undergo S-palmitoylation at a juxtamembrane cysteine residue, identified by a machine-learning topology-driven approach (TopoPalmTree) applied to the mouse transmembrane proteome; experimental assessment of Chodl as a candidate S-palmitoyl substrate was performed (results reported among confirmed candidates). Machine-learning prediction (TopoPalmTree), experimental S-palmitoylation assessment (method not fully detailed in abstract) The Journal of biological chemistry Low 39909380
2025 Sst-Chodl neurons (somatostatin and chondrolectin co-expressing GABAergic cells) are selectively active during low-arousal states; selective activation of Sst-Chodl cells is sufficient to promote multi-region cortical synchronization and induce sleep via long-range axons targeting multiple neocortical regions simultaneously. In vivo electrophysiology/calcium imaging, optogenetic selective activation of Sst-Chodl cells, behavioral sleep assays in mice bioRxivpreprint Medium bio_10.1101_2024.06.20.599756
2025 In a 15q13.3 microdeletion mouse model, single-nucleus transcriptomics showed the largest gene expression alterations in Sst_Chodl neurons; patch-clamp and calcium imaging revealed increased activity specifically in the Sst_Chodl subtype; chemogenetic inhibition of Sst_Chodl neurons rescued sleep disturbances in mutant mice. Single-nucleus RNA-seq (snRNA-seq), calcium imaging, patch-clamp electrophysiology, Patch-seq, chemogenetic inhibition (DREADD) with behavioral rescue Neuron Medium 40997796
2025 Conditional knockout of Chodl in embryonic myoblasts or adult satellite cells (SCs) does not affect muscle development but markedly impairs regeneration; Chodl-deficient SCs show reduced self-renewal, diminished proliferation, and impaired differentiation; a significant fraction of Chodl-null SCs mislocalize outside the basal lamina and undergo precocious activation, consistent with disrupted ECM and Notch signaling interactions. Conditional knockout mouse models (Cre-lox), single-cell RNA-seq, muscle injury regeneration assays, immunofluorescence for SC localization, in silico network perturbation analysis iScience High 40964242 42088368

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Integration of ATAC-seq and RNA-seq identifies human alpha cell and beta cell signature genes. Molecular metabolism 213 26977395
2010 Identification of novel spinal cholinergic genetic subtypes disclose Chodl and Pitx2 as markers for fast motor neurons and partition cells. The Journal of comparative neurology 99 20437528
2013 Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. Human molecular genetics 61 24067532
2001 From PREDs and open reading frames to cDNA isolation: revisiting the human chromosome 21 transcription map. Genomics 34 11707072
2025 Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Neuron 30 40403704
2002 Molecular cloning and characterization of human chondrolectin, a novel type I transmembrane protein homologous to C-type lectins. Genomics 25 12079284
2011 Chondrolectin is a novel diagnostic biomarker and a therapeutic target for lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 22 22016508
2012 Chondrolectin mediates growth cone interactions of motor axons with an intermediate target. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 22457492
2003 Isolation and characterization of chondrolectin (Chodl), a novel C-type lectin predominantly expressed in muscle cells. Gene 19 12711387
2018 Accumulation of poly(A) RNA in nuclear granules enriched in Sam68 in motor neurons from the SMNΔ7 mouse model of SMA. Scientific reports 14 29941967
2025 Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. bioRxiv : the preprint server for biology 12 39386678
2020 Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits. HGG advances 12 34734193
2003 A novel alternative spliced chondrolectin isoform lacking the transmembrane domain is expressed during T cell maturation. The Journal of biological chemistry 12 12621022
2024 Integrating single-cell and spatial transcriptomic analysis to unveil heterogeneity in high-grade serous ovarian cancer. Frontiers in immunology 9 38975339
2016 Expression of CHODL in hepatocellular carcinoma affects invasion and migration of liver cancer cells. Oncology letters 8 28356950
2008 The cytoplasmic domain of chondrolectin interacts with the beta-subunit of Rab geranylgeranyl transferase. Cellular & molecular biology letters 7 18161010
2007 Expression and localization of CHODLDeltaE/CHODLfDeltaE, the soluble isoform of chondrolectin. Cell biology international 7 17606388
2025 Topology-driven discovery of transmembrane protein S-palmitoylation. The Journal of biological chemistry 4 39909380
2025 Dysfunction of cortical GABAergic projection neurons as a major hallmark in a model of neuropsychiatric syndrome. Neuron 4 40997796
2025 Gut microbiota contribute to high-altitude adaptation in tree sparrows. mSystems 2 40742160
2025 Single-cell RNA sequencing of adult primate neocortex reveals the regulatory dynamics of neural plasticity. American journal of translational research 1 40385068
2025 Host Genetic Effects and Phenotypic Landscapes of Rumen Bacterial Enterotypes in a Large Sheep Population. Animals : an open access journal from MDPI 1 41007969
2026 Chondrolectin regulates the sublaminar localization and regenerative function of muscle satellite cells in mice. iScience 0 42088368
2025 Effects of melatonin treatment on germination, growth and physiological characteristics under drought stress in foxtail millet. Frontiers in plant science 0 40546432
2025 Chondrolectin regulates the sublaminar localization and regenerative function of muscle satellite cells in mice. bioRxiv : the preprint server for biology 0 40964242

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