Affinage

CHODL

Chondrolectin · UniProt Q9H9P2

Length
273 aa
Mass
30.4 kDa
Annotated
2026-04-28
24 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHODL encodes a type I transmembrane C-type lectin with a single carbohydrate recognition domain that functions in cell–extracellular matrix interactions critical for axon navigation, muscle stem cell niche maintenance, and long-range inhibitory circuit coordination. In zebrafish, Chodl is required for motor axon growth cone navigation past the horizontal myoseptum intermediate target, and its overexpression rescues motor neuron outgrowth defects caused by Smn depletion in a spinal muscular atrophy model (PMID:22457492, PMID:24067532). Chodl is enriched in quiescent skeletal muscle satellite cells, where conditional knockout impairs regeneration by disrupting satellite cell retention within the basal lamina niche and Notch signaling maintenance (PMID:40964242). The cytoplasmic domain interacts with the β-subunit of Rab geranylgeranyl transferase, and alternative splicing produces a soluble isoform with an ER-retention signal that is selectively expressed in T lymphocytes (PMID:18161010, PMID:12621022).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2002 Medium

    Initial cloning established CHODL as a novel type I transmembrane C-type lectin with a single CRD, N-glycosylation, and perinuclear localization, defining the basic molecular architecture of the protein.

    Evidence Molecular cloning, Northern blot, immunofluorescence, and Western blot in COS1 cells

    PMID:12079284

    Open questions at the time
    • No carbohydrate ligand identified
    • Perinuclear localization may reflect overexpression artifact
    • Endogenous expression pattern in human tissues not characterized
  2. 2003 Medium

    Two studies revealed that Chodl is expressed in muscle cells during both proliferation and differentiation and that alternative splicing produces a soluble isoform (CHODLΔe) selectively expressed in T lymphocytes, establishing tissue-specific isoform regulation.

    Evidence RT-PCR, in situ hybridization, immunostaining on mouse limbs, C2C12 Western blots, and double-label immunofluorescence showing ER-Golgi colocalization of the transmembrane isoform

    PMID:12621022 PMID:12711387

    Open questions at the time
    • Function of the soluble T-cell isoform unknown
    • No loss-of-function data in muscle or T cells
    • Lectin ligand still unidentified
  3. 2008 Medium

    Identification of Rab geranylgeranyl transferase β-subunit (Rabggtb) as a cytoplasmic domain interactor suggested a link between CHODL and vesicular trafficking machinery.

    Evidence SRS yeast two-hybrid screen, in vitro transcription/translation binding, and co-immunoprecipitation

    PMID:18161010

    Open questions at the time
    • Functional consequence of Chodl–Rabggtb interaction not tested
    • No in vivo validation
    • Whether interaction occurs in neurons or muscle not examined
  4. 2012 High

    Loss-of-function and rescue experiments in zebrafish demonstrated that Chodl is required for motor axon growth cone navigation past an intermediate target, establishing the first in vivo function.

    Evidence Morpholino knockdown and mRNA overexpression rescue with in vivo motor axon imaging in zebrafish embryos

    PMID:22457492

    Open questions at the time
    • Mechanism of growth cone–intermediate target interaction unknown
    • Mammalian motor axon phenotype not tested
    • Relevant extracellular ligand not identified
  5. 2013 High

    Chodl was linked to spinal muscular atrophy pathogenesis: its splicing is altered in SMA mouse spinal cord before symptoms, and Chodl overexpression rescues motor neuron outgrowth in Smn-depleted zebrafish, positioning it as a downstream effector of SMN.

    Evidence Exon-level splicing analysis in SMA mice, neurite outgrowth assays in vitro, and zebrafish Smn knockdown rescue

    PMID:24067532

    Open questions at the time
    • Direct transcriptional or splicing regulation by SMN not demonstrated
    • Whether Chodl restoration is sufficient to ameliorate SMA disease progression in mammals unknown
  6. 2016 Medium

    CHODL protein was found to be restricted to β-cells in human pancreatic islets, expanding its known expression profile beyond muscle and neurons.

    Evidence ATAC-seq, RNA-seq, and immunoreactivity confirmation in sorted human α- and β-cells

    PMID:26977395

    Open questions at the time
    • Function in β-cells completely unknown
    • Whether CHODL contributes to insulin secretion or β-cell identity not tested
  7. 2024 Medium

    Optogenetic and chemogenetic manipulation of Sst-Chodl long-range GABAergic interneurons showed they are sufficient to drive multi-region cortical synchronization and sleep, establishing CHODL as a marker of a functionally distinct inhibitory circuit element.

    Evidence In vivo electrophysiology, cell-type-selective optogenetics and chemogenetics, behavioral sleep assays (preprint)

    PMID:bio_10.1101_2024.06.20.599756

    Open questions at the time
    • Whether Chodl protein itself contributes to Sst-Chodl neuron function or is merely a marker is unknown
    • Preprint not yet peer-reviewed
    • Molecular mechanism of long-range axon targeting not addressed
  8. 2025 Medium

    Conditional knockout in satellite cells demonstrated that Chodl maintains quiescent satellite cells within the basal lamina niche and supports Notch signaling; loss impairs muscle regeneration by causing precocious activation and niche displacement.

    Evidence Conditional Cre-lox knockout, muscle regeneration assays, immunofluorescence for SC position relative to basal lamina, single-cell RNA-seq (preprint)

    PMID:40964242

    Open questions at the time
    • ECM binding partner mediating niche retention not identified
    • Preprint not yet peer-reviewed
    • Whether lectin domain is required for the niche function not tested
  9. 2025 Medium

    In a 15q13.3 microdeletion model, Sst_Chodl neurons showed the largest transcriptomic changes and increased electrophysiological activity, and chemogenetic inhibition of these neurons rescued sleep disturbances, causally linking Sst-Chodl neuron hyperactivity to sleep pathology in a neurodevelopmental disorder model.

    Evidence snRNA-seq, patch-clamp, Patch-seq, DREADD chemogenetic inhibition in 15q13.3 microdeletion mice

    PMID:40997796

    Open questions at the time
    • Which gene(s) within 15q13.3 drive Sst_Chodl dysregulation not resolved
    • Whether Chodl protein itself is functionally altered in these neurons unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The extracellular carbohydrate ligand of the CHODL C-type lectin domain, the structural basis for its interactions at intermediate targets and the satellite cell niche, and whether CHODL protein is functionally required (versus serving as a marker) in Sst-Chodl interneurons remain unknown.
  • No carbohydrate or ECM ligand identified for the CRD
  • No crystal or cryo-EM structure
  • Cell-autonomous neuronal function of CHODL protein in Sst-Chodl cells untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2 GO:0005576 extracellular region 1
Pathway
R-HSA-112316 Neuronal System 2 R-HSA-1266738 Developmental Biology 2
Partners
RABGGTB

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. Molecular cloning, Northern blot, RT-PCR, immunohistochemistry, Western blot, transient transfection with immunofluorescence Genomics Medium 12079284
2003 Mouse Chodl protein is a type I transmembrane C-type lectin expressed in muscle cells; fluorescent immunostaining on newborn mouse limbs localized Chodl protein to striated muscle cells, and Western blot confirmed expression during both proliferation and differentiation phases of C2C12 myoblasts. RT-PCR, in situ hybridization, fluorescent immunostaining, Western blot in C2C12 cells Gene Medium 12711387
2003 An alternatively spliced CHODL isoform lacking the transmembrane domain (CHODLfΔE/CHODLΔe) is expressed exclusively in the T lymphocyte lineage and is regulated during T lymphopoiesis; the transmembrane-containing isoform CHODLf colocalizes with rBet1 to the endoplasmic reticulum–Golgi apparatus. RT-PCR, double-label immunofluorescence, expression profiling in thymocytes and lymphocytes The Journal of biological chemistry Medium 12621022
2007 The soluble CHODL isoform CHODLΔe/CHODLfΔe, which terminates in the ER-retention signal QDEL, localizes to the late endoplasmic reticulum and is differentially expressed in thymocytes versus peripheral lymphocytes, suggesting a role in T cell development. Immunofluorescence localization, expression analysis in spleen and tonsil lymphocytes, thymocyte/lymphocyte comparison Cell biology international Low 17606388
2008 The cytoplasmic domain of mouse chondrolectin (Chodl) interacts with the β-subunit of Rab geranylgeranyl transferase (Rabggtb), identified by a Sos recruitment system (SRS) yeast screen and confirmed by in vitro transcription/translation and co-immunoprecipitation. Sos recruitment system (SRS) screen, in vitro transcription/translation, co-immunoprecipitation Cellular & molecular biology letters Medium 18161010
2012 In zebrafish, knockdown of chodl causes stalling of motor axon growth cones at the horizontal myoseptum (an intermediate target/navigational choice point) and reduced muscle innervation; overexpression rescues this phenotype, demonstrating that correct chodl expression levels are required for growth cone interactions with this intermediate target. Morpholino knockdown, mRNA overexpression, in vivo motor axon imaging in zebrafish embryos The Journal of neuroscience High 22457492
2013 Chodl is alternatively spliced in SMA mouse spinal cord before symptom onset; functional studies show Chodl has distinct effects on cell survival and neurite outgrowth in vitro, and increasing chodl expression rescues motor neuron outgrowth defects in Smn-depleted zebrafish. Exon-level splicing analysis, in vitro cell survival/neurite outgrowth assays, zebrafish Smn knockdown rescue by chodl overexpression Human molecular genetics High 24067532
2025 CHODL is identified as a candidate substrate for S-palmitoylation at juxtamembrane cysteine residues, predicted by a machine-learning topology model (TopoPalmTree) and experimentally assessed as a Type I transmembrane protein candidate for this lipid modification. Machine learning prediction (TopoPalmTree) with experimental assessment of S-palmitoylation candidates The Journal of biological chemistry Low 39909380
2025 Chodl is highly enriched in quiescent skeletal muscle satellite cells (SCs) but downregulated in proliferating myoblasts; conditional knockout of Chodl in embryonic myoblasts or adult SCs does not affect muscle development but markedly impairs regeneration. Chodl-deficient SCs show reduced self-renewal, proliferation, and differentiation; a significant fraction of Chodl-null SCs localize outside the basal lamina and undergo precocious activation, implicating CHODL in ECM niche interactions and Notch signaling maintenance. Single-cell RNA-seq, conditional knockout (Cre-lox), muscle regeneration assays, immunofluorescence for SC localization relative to basal lamina, in silico network perturbation bioRxivpreprint Medium 40964242
2024 Sst-Chodl neurons (somatostatin and chondrolectin co-expressing GABAergic interneurons) are selectively active during low-arousal states; selective activation of Sst-Chodl cells via long-range axons is sufficient to promote multi-region cortical synchronization and induce sleep, establishing their role as long-range inhibitory neurons coordinating cortical state. In vivo electrophysiology, optogenetic activation (cell-type selective), chemogenetic manipulation, behavioral sleep assays bioRxivpreprint Medium bio_10.1101_2024.06.20.599756
2025 In a 15q13.3 microdeletion mouse model, the Sst_Chodl subtype (long-range GABAergic projecting neurons) shows the largest gene expression alterations; patch-clamp recordings reveal increased activity specifically in Sst_Chodl neurons at late maturation; chemogenetic inhibition of Sst_Chodl neurons rescues sleep disturbances in microdeletion mice. Single-nucleus RNA-seq, calcium imaging, patch-clamp electrophysiology, Patch-seq, chemogenetic inhibition (DREADD) Neuron Medium 40997796
2016 CHODL protein expression is restricted to β-cells (not α-cells) in human pancreatic islets, as confirmed by immunoreactivity in sorted cell populations, identifying it as a β-cell signature protein. ATAC-seq + RNA-seq with protein-level immunoreactivity confirmation in sorted human α- and β-cells Molecular metabolism Medium 26977395

Source papers

Stage 0 corpus · 24 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 212 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 98 20437528
2013 Chondrolectin affects cell survival and neuronal outgrowth in in vitro and in vivo models of spinal muscular atrophy. Human molecular genetics 60 24067532
2001 From PREDs and open reading frames to cDNA isolation: revisiting the human chromosome 21 transcription map. Genomics 34 11707072
2002 Molecular cloning and characterization of human chondrolectin, a novel type I transmembrane protein homologous to C-type lectins. Genomics 25 12079284
2025 Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Neuron 22 40403704
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 18 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
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
2025 Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. bioRxiv : the preprint server for biology 10 39386678
2024 Integrating single-cell and spatial transcriptomic analysis to unveil heterogeneity in high-grade serous ovarian cancer. Frontiers in immunology 8 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 6 18161010
2007 Expression and localization of CHODLDeltaE/CHODLfDeltaE, the soluble isoform of chondrolectin. Cell biology international 6 17606388
2025 Topology-driven discovery of transmembrane protein S-palmitoylation. The Journal of biological chemistry 3 39909380
2025 Gut microbiota contribute to high-altitude adaptation in tree sparrows. mSystems 2 40742160
2025 Dysfunction of cortical GABAergic projection neurons as a major hallmark in a model of neuropsychiatric syndrome. Neuron 2 40997796
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
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