Affinage

CHL1

ATP-dependent DNA helicase DDX11 · UniProt Q96FC9

Length
970 aa
Mass
108.3 kDa
Annotated
2026-06-09
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHL1 (close homolog of L1) is a transmembrane immunoglobulin-superfamily cell adhesion molecule that organizes neuronal migration, axon guidance, dendrite orientation, and synaptic function through both proteolytically released ectodomain fragments and intracellular signaling complexes (PMID:22988240, PMID:22692213, PMID:18447583). Its extracellular domain is processed by two distinct proteases: ADAM8 sheds the ectodomain in the fibronectin domains, generating soluble fragments that promote neurite outgrowth and suppress neuronal death (PMID:14761956), while BACE1 cleaves CHL1 in vivo between Gln1061 and Asp1062, and loss of this processing reproduces CHL1-null axon guidance defects in hippocampal mossy fibers and olfactory projections, placing CHL1 downstream of BACE1 in axon targeting (PMID:22692213, PMID:22988240). The intracellular domain couples CHL1 to membrane and cytoskeletal machinery: it binds the clathrin-uncoating ATPase Hsc70 to target it to synapses and drive clathrin-coated synaptic vesicle recycling (PMID:17178404), recruits the ERM protein ezrin via an RGGKYSV motif to mediate Sema3A-induced growth cone collapse and neurite outgrowth (PMID:17995939), and associates with βII spectrin, with ligand-induced clustering triggering Cys1102 palmitoylation and lipid-raft-dependent endocytosis required for neurite outgrowth (PMID:23144456). CHL1 acts through a network of heterophilic partners—NB-3/PTPα to orient apical dendrites, EphA7 (cooperating with L1) for thalamocortical EphrinA5 responses, vitronectin and the PAI-2/uPA/integrin system for migration and neuritogenesis, and the 5-HT2c receptor to modulate its phosphorylation and behavioral output—as well as homophilic CHL1-CHL1 interactions that organize cerebellar stellate axons along Bergmann glial fibers and guide dopaminergic axon pathfinding (PMID:18046458, PMID:20576928, PMID:25355214, PMID:26527397, PMID:18447583, PMID:28839197). Survival and proliferative signaling proceed through PI3K and MEK/ERK pathways, with CHL1 negatively regulating neural progenitor proliferation via ERK1/2 (PMID:15880726, PMID:20933598). After CNS injury, reactive astrocytes upregulate CHL1 through PI3K/PKCδ/ERK/NF-κB signaling, creating a glial-scar component that restricts axonal regeneration (PMID:17611275, PMID:19672967). In epithelial tumors CHL1 acts as a suppressor, binding Integrin-β1 and Merlin to inactivate integrin-β1/AKT and Rho-family GTPase signaling (PMID:31523184, PMID:29899830).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Established that the CHL1 ectodomain is not merely adhesive but actively pro-survival, raising the question of how a cell adhesion molecule signals neuronal survival.

    Evidence CHL1-Fc fusion protein rescue of cerebellar granule and hippocampal neuron apoptosis in serum-free culture, with Bcl-2 induction by Western blot

    PMID:10022583

    Open questions at the time
    • Receptor mediating the survival effect not identified
    • Bcl-2 link is a single-method correlation
  2. 2004 High

    Identified the protease that converts membrane CHL1 into the bioactive soluble form, defining ADAM8 as the ectodomain sheddase and linking cleavage to outgrowth and survival.

    Evidence In vitro cleavage of CHL1-Fc, ADAM8 active-site mutagenesis, ADAM8-deficient brain extracts, and neurite/cell-death assays with cerebellar neurons

    PMID:14761956

    Open questions at the time
    • Physiological stimulus triggering ADAM8 shedding unknown
    • Receptor for shed CHL1 fragments not defined
  3. 2005 Medium

    Dissected the intracellular signaling required for CHL1-mediated survival, showing dependence on PI3K and MEK/ERK.

    Evidence Picomolar CHL1-Fc rescue of purified motoneurons blocked by LY294002 and PD98059

    PMID:15880726

    Open questions at the time
    • Upstream receptor coupling CHL1 to PI3K/ERK not identified
    • Single pharmacological experiment set
  4. 2006 High

    Defined an intracellular function for CHL1 by identifying Hsc70 binding, establishing CHL1 as a synaptic targeting cue for clathrin-coated vesicle recycling.

    Evidence Binding-partner identification, CHL1 knockout mice, biochemical fractionation, EM, and FM dye uptake/release at synaptic boutons

    PMID:17178404

    Open questions at the time
    • Structural basis of CHL1-Hsc70 binding not resolved
    • Regulation of the interaction by activity unclear
  5. 2007 High

    Mapped CHL1's cytoplasmic signaling to ERM proteins and established the heterophilic and homophilic adhesion partners coordinating dendrite orientation and axon organization.

    Evidence Cytoplasmic-domain mutagenesis defining the RGGKYSV ezrin-recruitment motif with Sema3A/outgrowth assays; co-IP of NB-3 and PTPα with multiple KO mouse lines; Bergmann glial localization with stellate axon analysis in CHL1-/- mice

    PMID:17995939 PMID:18046458 PMID:18447583

    Open questions at the time
    • How ERM recruitment links to specific cytoskeletal outputs not fully defined
    • PTPα substrates downstream of the complex unknown
  6. 2007 High

    Revealed an injury-context role: reactive astrocytes upregulate CHL1 to restrict axon regeneration via homophilic interactions, with consequences for functional recovery.

    Evidence CHL1-/- spinal cord injury model with locomotor scoring, bFGF-stimulated astrocyte cultures with FGFR/ERK/CaMKII/PI3K inhibitors, and neuron-astrocyte cocultures

    PMID:17611275

    Open questions at the time
    • Neuronal receptor mediating growth inhibition not identified beyond homophilic CHL1
    • Relative contribution of glial scar vs other inhibitors unquantified
  7. 2009 Medium

    Showed CHL1 cooperates with PAK1-3 kinases in shaping the leading process/apical dendrite, indicating parallel cooperating cytoskeletal pathways.

    Evidence In utero electroporation of dominant-negative PAK into CHL1-/- cortex with quantitative morphology

    PMID:19819308

    Open questions at the time
    • Whether CHL1 and PAK physically interact untested
    • Single experimental approach
  8. 2010 High

    Extended CHL1's repertoire to thalamocortical guidance via selective EphA7 association and epistatic cooperation with L1.

    Evidence Co-IP of CHL1 with EphA7 and double CHL1-/-/L1-/y mutant mice with EphrinA5 growth cone collapse assays

    PMID:20576928

    Open questions at the time
    • Functional consequence of CHL1-EphA7 binding on Eph signaling not measured
    • Mechanism of CHL1/L1 cooperation unresolved
  9. 2010 Medium

    Defined CHL1 as a negative regulator of neural progenitor proliferation and the astrocytic signaling cascade controlling its own expression.

    Evidence CHL1-/- NPC proliferation/differentiation assays with ERK1/2 inhibition; astrocyte cultures dissecting PI3K/PKCδ/ERK/NF-κB control of CHL1 upregulation

    PMID:19672967 PMID:20933598

    Open questions at the time
    • How CHL1 engages ERK1/2 in progenitors mechanistically unclear
    • Transcription factors directly driving the CHL1 gene not identified
  10. 2012 High

    Identified BACE1 as a second, physiological protease cleaving CHL1 and connected this processing to specific axon guidance phenotypes.

    Evidence Neuronal secretome proteomics, BACE1 KO mice, pharmacological BACE1 inhibition, MS cleavage-site mapping (Gln1061-Asp1062), and phenotypic comparison of BACE1-/- and CHL1-/- mice

    PMID:22692213 PMID:22988240

    Open questions at the time
    • Fate and receptor of the BACE1-generated fragment undefined
    • Relationship between ADAM8 and BACE1 cleavage not reconciled
  11. 2012 High

    Linked CHL1 ligand-induced clustering to palmitoylation-dependent endocytosis via βII spectrin, providing a trafficking mechanism for outgrowth signaling.

    Evidence Co-IP of CHL1 with βII spectrin, lipid raft fractionation, C1102 mutagenesis, raft disruption, nifedipine treatment, and neurite outgrowth assays

    PMID:23144456

    Open questions at the time
    • Palmitoyltransferase acting on Cys1102 not identified
    • How endocytosis converts to outgrowth signaling unresolved
  12. 2014 High

    Resolved stage-specific use of homophilic vs heterophilic adhesion, adding vitronectin and the PAI-2/uPA/integrin system as extracellular partners for migration and neuritogenesis.

    Evidence Co-IP/colocalization, function-blocking antibodies, CHL1 RGD-peptide inhibition, and cerebellar migration/outgrowth assays with CHL1-/- comparison

    PMID:25355214

    Open questions at the time
    • Which integrin heterodimers CHL1 engages not specified
    • Direct vs indirect vitronectin binding not structurally defined
  13. 2015 Medium

    Extended CHL1 to receptor signaling regulation by showing it binds the 5-HT2c receptor and controls its phosphorylation and effector coupling, with behavioral consequences.

    Evidence Co-IP and peptide binding with the 5-HT2c third intracellular loop, CHL1-/- behavior, and phosphorylation/PTEN/β-arrestin 2 assays

    PMID:26527397

    Open questions at the time
    • Stoichiometry and structural interface of the interaction unknown
    • Causal chain from receptor modulation to behavior incomplete
  14. 2017 Medium

    Demonstrated cell-type-selective homophilic CHL1 signaling in dopaminergic neuron development, governing migration, extension, and repulsion.

    Evidence VM expression mapping, primary DA neuron cultures on CHL1 substrates, and function-blocking antibody assays

    PMID:28839197

    Open questions at the time
    • Homophilic interaction inferred from blocking rather than direct binding
    • Downstream signaling in DA neurons not defined
  15. 2018 Medium

    Established a tumor-suppressor role for CHL1 in neuroblastoma acting through MAPK/Akt and Rho-GTPase inhibition.

    Evidence Inducible overexpression/knockdown, neurite/colony/migration assays, orthotopic xenografts, and pathway Western blots with Rho pull-downs

    PMID:29899830

    Open questions at the time
    • Membrane partner transducing the suppressor effect not identified
    • Single-lab tumor model
  16. 2019 Medium

    Identified the Integrin-β1/Merlin axis as the mechanism of CHL1 tumor suppression in epithelial cancer and added CHL1 trans-heterophilic guidance of dopaminergic axons.

    Evidence Co-IP of CHL1 with Integrin-β1 and Merlin plus xenograft and EMT/Rho assays in NPC; ALCAM-substrate mDA cultures with CHL1/Nrp1/L1cam neutralizing antibodies and semaphorin assays

    PMID:31300520 PMID:31523184

    Open questions at the time
    • Whether the same Integrin-β1/Merlin axis operates in neurons untested
    • Direct binding partners for the ALCAM/semaphorin responses not biochemically resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the neuronal receptor(s) transducing signals from shed/soluble CHL1 fragments, and how ADAM8 and BACE1 cleavage events are coordinated, remain unresolved.
  • No receptor identified for ADAM8- or BACE1-released CHL1 ectodomain fragments
  • Structural basis of most intracellular and extracellular CHL1 interactions undetermined
  • Integration of the multiple parallel signaling pathways (ERM, Hsc70, spectrin, integrin) into a unified model lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098631 cell adhesion mediator activity 4 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
ADAM8BACE1EPHA7EZRHSPA8ITGB1NB-3PTPRA

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 CHL1 (the neural cell adhesion molecule close homolog of L1) is cleaved by the protease BACE1 in vivo under physiological conditions. The BACE1 cleavage site on CHL1 was determined by mass spectrometry to be between Gln(1061) and Asp(1062) in the membrane-proximal region. Quantitative proteomics of neuronal secretome after BACE1 inhibition; genetic BACE1 knockout mice; pharmacological BACE1 inhibition in mice and cell cultures; mass spectrometry for cleavage site mapping The Journal of biological chemistry High 22692213 22988240
2012 BACE1 deficiency in mice produces axon guidance defects (shortened and disorganized infrapyramidal bundle of hippocampal mossy fibers; olfactory sensory neuron projection defects) that are strikingly similar to those in CHL1-deficient mice, establishing that these BACE1-/- phenotypes result from abrogated BACE1 processing of CHL1. BACE1 and CHL1 co-localize in hippocampal mossy fiber terminals, olfactory sensory neuron axons, and growth cones of primary hippocampal neurons. BACE1 knockout mouse phenotypic analysis; CHL1-/- mouse comparison; immunohistochemistry and co-localization; biochemical processing assays in hippocampus and olfactory bulb The Journal of biological chemistry High 22692213 22988240
2004 CHL1 ectodomain shedding is performed by the metalloprotease-disintegrin ADAM8, which cleaves a CHL1-Fc fusion protein in vitro at two sites in fibronectin domains II (125 kDa fragment) and V (165 kDa fragment). Cleavage was inhibited by the metalloprotease inhibitor batimastat, was not observed with catalytically inactive ADAM8 (E330Q mutant), and was absent in brain extracts of ADAM8-deficient mice. Soluble CHL1 processed by ADAM8 promoted neurite outgrowth and suppressed neuronal cell death; these effects were not observed with inactive ADAM8, ADAM10, or ADAM17. In vitro cleavage assay with CHL1-Fc fusion protein; site-directed mutagenesis of ADAM8 active site; ADAM8-deficient mouse brain extracts; cell transfection; co-culture with cerebellar granule neurons; neurite outgrowth and cell death assays The Journal of biological chemistry High 14761956
2006 The intracellular domain of CHL1 binds to the clathrin-uncoating ATPase Hsc70. CHL1 functions as a synaptic targeting cue for Hsc70; CHL1 deficiency or disruption of the CHL1/Hsc70 complex reduces Hsc70 targeting to synaptic membranes and vesicles, causes accumulation of abnormally high levels of clathrin-coated synaptic vesicles with reduced ability to release clathrin, and impairs activity-dependent clathrin-coated vesicle generation and FM dye uptake/release, revealing a role for CHL1 in clathrin-dependent synaptic vesicle recycling. Yeast two-hybrid / binding partner identification; CHL1 gene ablation in mice; biochemical fractionation; electron microscopy; FM dye uptake/release assays in synaptic boutons Neuron High 17178404
2007 CHL1 recruits ezrin (an ERM family member) to the plasma membrane through a membrane-proximal cytoplasmic motif (RGGKYSV). This CHL1/ERM interaction is required for Sema3A-induced growth cone collapse, CHL1-dependent neurite outgrowth and branching in cortical neurons, haptotactic cell migration, and cellular adhesion to fibronectin. Cytofluorescence recruitment assay; deletion and point mutagenesis of cytoplasmic domain; Sema3A growth cone collapse assay; neurite outgrowth and branching assay; cell migration and adhesion assay in cortical embryonic neurons Journal of neurochemistry High 17995939
2007 CHL1 directly associates with NB-3 (a member of the F3/contactin family) and enhances NB-3 cell surface expression. CHL1 and NB-3 both interact with protein tyrosine phosphatase alpha (PTPα) and regulate its activity. Loss of CHL1, NB-3, or PTPα leads to aberrant/misoriented apical dendrite projections of deep-layer pyramidal neurons in the visual cortex, indicating a CHL1–NB-3–PTPα signaling complex regulates apical dendrite orientation. Co-immunoprecipitation; cell surface expression assays; PTPα activity assay; CHL1-/-, NB-3-/-, and PTPα-/- mouse analysis; confocal microscopy of cortical neurons The EMBO journal High 18046458
2010 CHL1 associates selectively with EphA7 (whereas L1 associates with EphA3, EphA4, and EphA7), as shown by co-immunoprecipitation. L1 and CHL1 cooperate in repellent responses to EphrinA5 for thalamic axon guidance; double CHL1-/-/L1-/y mutant mice show a striking posterior shift of motor thalamic axons to visual cortex not seen in single mutants, demonstrating epistatic cooperation between CHL1 and L1 in thalamocortical targeting. Co-immunoprecipitation; double-mutant mouse generation and analysis; growth cone collapse assays with EphrinA5; immunofluorescence colocalization Cerebral cortex High 20576928
2014 CHL1 interacts with vitronectin and plasminogen activator inhibitor-2 (PAI-2) as novel extracellular binding partners. CHL1-induced cerebellar neurite outgrowth and neuronal migration depend on vitronectin-mediated integrin signaling (involving an RGD motif in CHL1) and on PAI-2/uPA/uPA receptor/integrin pathways. At earlier postnatal stages, homophilic CHL1-CHL1 trans-interactions regulate neuronal progenitor differentiation, whereas heterophilic interactions with vitronectin and the plasminogen activator system regulate neuritogenesis and migration at later stages. Co-immunoprecipitation / colocalization; function-blocking antibodies against vitronectin, PAI-2, uPA, uPA receptor, integrins; CHL1-derived RGD peptide inhibition; cerebellar granule cell migration and neurite outgrowth assays; CHL1-/- mouse comparison The Journal of neuroscience High 25355214
1999 CHL1-Fc fusion protein (extracellular domain of CHL1 fused to human IgG Fc) significantly enhanced survival of cerebellar granule neurons and hippocampal neurons undergoing apoptosis in serum-free culture (~45% increase), both in soluble form and as substrate. Bcl-2 protein levels in cerebellar granule neurons were increased by L1-Fc treatment, implicating Bcl-2 as an intracellular mediator. Neuronal apoptosis assay in serum-free medium; CHL1-Fc fusion protein treatment; Western blot for Bcl-2 and c-Jun Journal of neurobiology Medium 10022583
2005 CHL1-Fc fusion protein promotes survival of purified embryonic motoneurons at picomolar concentrations (similar to L1-Fc). CHL1-induced motoneuron survival is completely inhibited by LY294002 (PI3K inhibitor) and PD98059 (MEK inhibitor), indicating that both PI3K and MEK/ERK pathways are required for CHL1-mediated survival signaling. Purified motoneuron survival assay; pharmacological inhibition of PI3K (LY294002) and MEK (PD98059); dose-response analysis with CHL1-Fc fusion protein Journal of neuroscience research Medium 15880726
2007 CHL1 is localized to apical Bergmann glial (BG) fibers and stellate cells during cerebellar development. In CHL1-/- mice, stellate axons deviate from BG fibers and show aberrant branching and orientation; synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. This establishes CHL1 as a molecular signal on BG fibers that organizes GABAergic stellate axon arbors and directs their dendritic innervation. GFP BAC transgenic reporter mice; CHL1-/- mouse analysis; immunofluorescence localization; electron microscopy of synapses; confocal microscopy of axon morphology PLoS biology High 18447583
2007 CHL1 upregulation in GFAP-positive reactive astrocytes (glial scar) after spinal cord injury restricts axonal growth and remodeling. This upregulation is induced by basic FGF (bFGF) and is abolished by inhibitors of FGF receptor-dependent ERK, CaMKII, and PI3K signaling pathways. Homophilic CHL1-CHL1 interactions between neurons and astrocytes mediate reduced neurite outgrowth. CHL1-/- mice show improved functional recovery after spinal cord injury compared to wild-type, associated with enhanced monoaminergic reinnervation. CHL1-/- mouse spinal cord injury model; locomotor rating and video analysis; immunohistochemistry; primary astrocyte cultures with bFGF stimulation; pharmacological inhibitor studies; heterogenotypic neuron-astrocyte cocultures The Journal of neuroscience High 17611275
2010 CHL1 deficiency enhances proliferation and self-renewal of neural progenitor cells (NPCs) and promotes neuronal differentiation. CHL1 negatively regulates NPC proliferation through activation of the ERK1/2 MAPK pathway; pharmacological inhibition of ERK1/2 eliminates the increased proliferation seen in CHL1-/- NPCs. CHL1-/- mouse brain analysis (BrdU incorporation in SVZ, Tuj1 staining in cortical plate); primary NPC cultures from CHL1-/- and wild-type mice; ERK1/2 MAPK pharmacological inhibition; proliferation and differentiation assays Molecular and cellular neurosciences Medium 20933598
2012 Neuritogenesis-promoting ligand-dependent clustering of CHL1 induces palmitoylation and lipid raft-dependent endocytosis of CHL1. βII spectrin was identified as a binding partner of CHL1; partial disruption of the CHL1-βII spectrin complex accompanies CHL1 endocytosis. Mutation of cysteine 1102 within the CHL1 intracellular domain reduces lipid raft association and endocytosis. CHL1-dependent neurite outgrowth requires lipid raft assembly, voltage-dependent Ca2+ channels, and the CHL1 Cys-1102 palmitoylation site. Co-immunoprecipitation of CHL1 and βII spectrin; lipid raft fractionation; site-directed mutagenesis (C1102); pharmacological disruption of lipid rafts; nifedipine (L-type Ca2+ channel inhibitor) treatment; endocytosis assays; neurite outgrowth assays The Journal of biological chemistry High 23144456
2009 CHL1 cooperates with PAK1-3 kinases in regulating morphological development of the leading process/apical dendrite of embryonic cortical neurons. Dominant-negative PAK inhibition in CHL1-/- mouse cortex caused extreme branching in the intermediate zone and cortical plate, far exceeding effects in either mutant alone, consistent with CHL1 and PAK1-3 acting in independent but cooperating pathways. In utero electroporation of dominant-negative PAK1 AID construct into CHL1-/- and wild-type embryos; confocal microscopy of GFP-labeled neurons in slice culture; quantitative morphological analysis Neuroscience Medium 19819308
2015 CHL1 binds to a peptide stretch in the third intracellular loop of the serotonin 2c (5-HT2c) receptor through its own intracellular domain. CHL1 regulates 5-HT2c receptor phosphorylation and the receptor's association with PTEN and β-arrestin 2. CHL1-deficient mice show 5-HT2c-receptor-related reduction in locomotor activity and reactivity to novelty. CHL1 modulates signaling pathways triggered by constitutively active 5-HT2c receptor isoforms. CHL1 and 5-HT2c receptor co-localize in striatal and hippocampal GABAergic neurons. Co-immunoprecipitation of CHL1 with 5-HT2c receptor; peptide binding assay; CHL1-/- mouse behavioral analysis; immunofluorescence colocalization; phosphorylation and co-IP assays with PTEN and β-arrestin 2 Journal of cell science Medium 26527397
2010 CHL1 expression in astrocytes is upregulated via a PI3K/PKCδ/ERK1/2/NF-κB signaling cascade. LPS-induced astrogliosis triggers PKCδ translocation to the membrane, ERK1/2 phosphorylation downstream of PKCδ, and NF-κB nuclear translocation, all of which are required for upregulation of CHL1 protein expression. The NO-guanylate cyclase-cGMP pathway, by contrast, does not mediate this upregulation. LPS-induced CHL1 upregulation in reactive astrocytes inhibits hippocampal neurite outgrowth in coculture. Primary mouse astrocyte cultures; pharmacological inhibition of PI3K, PKCδ, ERK1/2, NF-κB; PKCδ genetic knockdown; subcellular fractionation; Western blot; neurite outgrowth coculture assay Glia Medium 19672967
2019 CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by directly interacting with Integrin-β1 and linking to Merlin, leading to inactivation of the integrin β1-AKT signaling pathway. CHL1 also induces mesenchymal-epithelial transition (MET) and inactivates RhoA/Rac1/Cdc42 signaling, inhibiting stress fiber, lamellipodia, and filopodia formation. Co-immunoprecipitation of CHL1 with Integrin-β1 and Merlin; ectopic CHL1 expression in NPC cells; colony formation, cell motility, and invasion assays; Western blot for EMT markers and Rho GTPase pathway; in vivo xenograft experiments International journal of biological sciences Medium 31523184
2018 CHL1 acts as a tumor suppressor in neuroblastoma: overexpression of CHL1 induces neurite-like outgrowth and markers of neuronal differentiation, inhibits anchorage-independent colony formation, and suppresses tumor xenograft growth. Knockdown of CHL1 activates Rho GTPases, enhances proliferation and migration, and accelerates orthotopic xenograft growth. CHL1 functions through inhibition of MAPK and Akt pathways. Inducible CHL1 overexpression and knockdown cell models; neurite outgrowth assay; colony formation; Transwell migration; orthotopic xenograft mouse model; Western blot for MAPK/Akt pathway components; Rho GTPase pull-down assay Oncotarget Medium 29899830
2019 CHL1 mediates axonal growth promotion of midbrain dopamine (mDA) neurons through trans-heterophilic interactions. The growth-promoting effect of ALCAM substrate on mDA neurons was abolished by neutralizing antibodies against Chl1 (as well as Nrp1 and L1cam), and CHL1 modulates the response of mDA neurites to soluble semaphorins (abolishing Sema3A growth promotion; inducing branching in the presence of Sema3C). Primary midbrain cultures on ALCAM substrate; function-blocking antibodies against CHL1, Nrp1, L1cam; neurite growth and branching assays; semaphorin stimulation experiments The Journal of neuroscience Medium 31300520
2017 CHL1 mediates homophilic CHL1-CHL1 interactions that regulate VM dopaminergic progenitor migration, differentiation, axonal extension, and axonal repulsion (selectively in DA neurons). Both substrate-bound and soluble forms of CHL1 have distinct functional roles in DA neuron development. Temporal and spatial CHL1 expression mapping in VM; primary VM DA neuron cultures on CHL1 substrates; function-blocking antibodies against CHL1; neurite extension and repulsion assays; DA progenitor migration assays Scientific reports Medium 28839197

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 The variant call format and VCFtools. Bioinformatics (Oxford, England) 10856 21653522
2013 Frailty consensus: a call to action. Journal of the American Medical Directors Association 2896 23764209
2009 CHL1 functions as a nitrate sensor in plants. Cell 943 19766570
2007 Regenerative endodontics: a review of current status and a call for action. Journal of endodontics 592 17368324
2015 A Call for Systematic Research on Solute Carriers. Cell 460 26232220
2021 Resveratrol (RV): A pharmacological review and call for further research. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 351 34649335
2008 Environmental epigenetics and asthma: current concepts and call for studies. American journal of respiratory and critical care medicine 196 18187692
2024 Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy. Journal of hematology & oncology 167 38863020
2006 Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. American journal of respiratory and critical care medicine 156 17053206
2012 The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo. The Journal of biological chemistry 149 22692213
1999 Prevention of neuronal cell death by neural adhesion molecules L1 and CHL1. Journal of neurobiology 148 10022583
2012 β-Site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1)-deficient mice exhibit a close homolog of L1 (CHL1) loss-of-function phenotype involving axon guidance defects. The Journal of biological chemistry 129 22988240
2012 MicroRNA-10a targets CHL1 and promotes cell growth, migration and invasion in human cervical cancer cells. Cancer letters 124 22634495
2017 Progress towards a public chemogenomic set for protein kinases and a call for contributions. PloS one 116 28767711
2016 Plant Enhancers: A Call for Discovery. Trends in plant science 107 27593567
2004 Ectodomain shedding of the neural recognition molecule CHL1 by the metalloprotease-disintegrin ADAM8 promotes neurite outgrowth and suppresses neuronal cell death. The Journal of biological chemistry 107 14761956
2008 Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites. PLoS biology 103 18447583
2000 Differential expression of COUP-TFI, CHL1, and two novel genes in developing neocortex identified by differential display PCR. The Journal of neuroscience : the official journal of the Society for Neuroscience 101 11027229
2018 Cancer genetics, precision prevention and a call to action. Nature genetics 98 30158684
2004 Developing DNA vaccines that call to dendritic cells. The Journal of clinical investigation 92 15520855
2007 Glial scar expression of CHL1, the close homolog of the adhesion molecule L1, limits recovery after spinal cord injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 17611275
2000 Clues to patients' explanations and concerns about their illnesses. A call for active listening. Archives of family medicine 91 10728107
2014 MicroRNA-590 promotes cervical cancer cell growth and invasion by targeting CHL1. Journal of cellular biochemistry 77 24288179
2011 Differential expression of CHL1 gene during development of major human cancers. PloS one 75 21408220
2006 The adhesion molecule CHL1 regulates uncoating of clathrin-coated synaptic vesicles. Neuron 75 17178404
2000 Expression of CHL1 and L1 by neurons and glia following sciatic nerve and dorsal root injury. Molecular and cellular neurosciences 75 10882484
2007 Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation in the neocortex via PTP alpha. The EMBO journal 74 18046458
2014 FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy. World journal of gastroenterology 69 25132748
2016 The Preoperative Sinus CT: Avoiding a "CLOSE" Call with Surgical Complications. Radiology 68 27643765
2017 microRNAs Make the Call in Cancer Personalized Medicine. Frontiers in cell and developmental biology 65 29018797
2011 Molecular call and response: the physiology of bacterial small RNAs. Biochimica et biophysica acta 61 21843668
2017 A wake-up call to quiescent cancer cells - potential use of DYRK1B inhibitors in cancer therapy. The FEBS journal 60 29193696
2018 The African Esophageal Cancer Consortium: A Call to Action. Journal of global oncology 58 30241229
2005 Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population. Schizophrenia research 58 15653271
2007 A call to arms: coevolution of animal viruses and host innate immune responses. Trends in genetics : TIG 57 17467114
2004 Call for an enzyme genomics initiative. Genome biology 57 15287973
2021 Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence. Journal of molecular medicine (Berlin, Germany) 55 34800164
2016 Melanoma: Last call for radiotherapy. Critical reviews in oncology/hematology 51 28109401
2021 Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway. Cell death & disease 50 34718336
2014 Fluorescent sensors for activity and regulation of the nitrate transceptor CHL1/NRT1.1 and oligopeptide transporters. eLife 50 24623305
2011 Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker. Pharmacogenomics 50 21332311
2007 CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane. Journal of neurochemistry 50 17995939
2018 Translational Research in Cardiovascular Repair: A Call for a Paradigm Shift. Circulation research 49 29348252
2010 L1 and CHL1 Cooperate in Thalamocortical Axon Targeting. Cerebral cortex (New York, N.Y. : 1991) 49 20576928
2004 Workshop on Alcohol Use and Health Disparities 2002: a call to arms. Alcohol (Fayetteville, N.Y.) 49 15066702
2023 A pharmacological review on SIRT 1 and SIRT 2 proteins, activators, and inhibitors: Call for further research. International journal of biological macromolecules 48 37105251
2006 Repulsion or adhesion: receptors make the call. Current opinion in cell biology 48 16930978
2018 Overexpression of miR-21-5p promotes proliferation and invasion of colon adenocarcinoma cells through targeting CHL1. Molecular medicine (Cambridge, Mass.) 45 30134821
2003 Call volume and insulin signaling. International review of cytology 45 12696593
2021 Omicron: Call for updated vaccines. Journal of medical virology 43 34927258
2014 Interaction of the cell adhesion molecule CHL1 with vitronectin, integrins, and the plasminogen activator inhibitor-2 promotes CHL1-induced neurite outgrowth and neuronal migration. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 25355214
2014 miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma. Biochemical and biophysical research communications 41 24971532
2022 DNA barcoding of Cymbidium by genome skimming: Call for next-generation nuclear barcodes. Molecular ecology resources 40 36219539
2025 Treatment of patients with IgA nephropathy: a call for a new paradigm. Kidney international 39 39894081
2015 Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene. Journal of neurochemistry 39 26285062
2013 CHL1 is involved in human breast tumorigenesis and progression. Biochemical and biophysical research communications 39 23906755
2019 Schizophrenia as a pseudogenetic disease: A call for more gene-environmental studies. Psychiatry research 37 31200193
2017 The roles of call wall invertase inhibitor in regulating chilling tolerance in tomato. BMC plant biology 37 29121866
2016 Unsolved matters in leprosy: a descriptive review and call for further research. Annals of clinical microbiology and antimicrobials 36 27209077
2013 Chl1 DNA helicase regulates Scc2 deposition specifically during DNA-replication in Saccharomyces cerevisiae. PloS one 36 24086532
2012 The phosphatidylinositol 4-kinases: don't call it a comeback. Sub-cellular biochemistry 36 22403072
2000 CHL1 is a nuclear protein with an essential ATP binding site that exhibits a size-dependent effect on chromosome segregation. Nucleic acids research 36 10931920
2014 Managing chronic pain in adults with haemophilia: current status and call to action. Haemophilia : the official journal of the World Federation of Hemophilia 34 25274075
1997 Characterization of putative human homologues of the yeast chromosome transmission fidelity gene, CHL1. The Journal of biological chemistry 34 9013641
2010 CHL1 negatively regulates the proliferation and neuronal differentiation of neural progenitor cells through activation of the ERK1/2 MAPK pathway. Molecular and cellular neurosciences 33 20933598
2006 Obtaining and screening compound collections: a user's guide and a call to chemists. Current opinion in chemical biology 33 16677847
2023 Spotlight on Genetic Kidney Diseases: A Call for Drug Delivery and Nanomedicine Solutions. ACS nano 32 36988207
2021 Recognizing the ethical implications of stem cell research: A call for broadening the scope. Stem cell reports 31 34214488
2021 Exosomal lncRNA CHL1-AS1 Derived from Peritoneal Macrophages Promotes the Progression of Endometriosis via the miR-610/MDM2 Axis. International journal of nanomedicine 31 34408418
2012 Lipid raft-dependent endocytosis of close homolog of adhesion molecule L1 (CHL1) promotes neuritogenesis. The Journal of biological chemistry 31 23144456
2005 Neural adhesion molecules L1 and CHL1 are survival factors for motoneurons. Journal of neuroscience research 31 15880726
2004 A call for replicating vector prime-protein boost strategies in HIV vaccine design. Expert review of vaccines 31 15285710
2019 Axonal Growth of Midbrain Dopamine Neurons is Modulated by the Cell Adhesion Molecule ALCAM Through Trans-Heterophilic Interactions with L1cam, Chl1, and Semaphorins. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 31300520
2019 The cell stress response: extreme times call for post-transcriptional measures. Wiley interdisciplinary reviews. RNA 30 31755249
2021 Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune. Cellular and molecular life sciences : CMLS 29 34296319
2020 An appraisal of allergic disorders in India and an urgent call for action. The World Allergy Organization journal 29 32774662
2018 CHL1 gene acts as a tumor suppressor in human neuroblastoma. Oncotarget 28 29899830
2018 DYSLIPIDEMIA IN MEXICO, A CALL FOR ACTION. Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion 28 30307444
2009 CHL1 cooperates with PAK1-3 to regulate morphological differentiation of embryonic cortical neurons. Neuroscience 28 19819308
2000 The cell recognition molecule CHL1 is strongly upregulated by injured and regenerating thalamic neurons. The Journal of comparative neurology 28 10972939
2021 Anal cancer and precancerous lesions: a call for improvement. The lancet. Gastroenterology & hepatology 27 33714370
2021 The ethics of human-embryoids model: a call for consistency. Journal of molecular medicine (Berlin, Germany) 27 33792755
1996 The human homologue of the yeast CHL1 gene is a novel keratinocyte growth factor-regulated gene. The Journal of biological chemistry 27 8798685
2018 A call for more science in forensic science. Proceedings of the National Academy of Sciences of the United States of America 26 29650539
2015 Cervical cancer control in Latin America: A call to action. Cancer 26 26670695
2025 SPP1 macrophages across diseases: A call for reclassification? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 40047497
2024 Brain incoming call from glia during neuroinflammation: Roles of extracellular vesicles. Neurobiology of disease 25 39251030
2003 Altered expression of CHL1 by glial cells in response to optic nerve injury and intravitreal application of fibroblast growth factor-2. Journal of neuroscience research 25 12605410
2013 Cutaneous toxicities of BRAF inhibitors: clinical and pathological challenges and call to action. Critical reviews in oncology/hematology 23 23830782
2010 Phosphatidylinositol 3-kinase/protein kinase Cdelta activation induces close homolog of adhesion molecule L1 (CHL1) expression in cultured astrocytes. Glia 23 19672967
2019 Aberrant expression of CHL1 gene and long non-coding RNA CHL1-AS1, CHL1-AS2 in ovarian endometriosis. European journal of obstetrics, gynecology, and reproductive biology 22 30943448
2017 Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways. Scientific reports 22 28839197
2022 Review of Cerebrospinal Fluid Physiology and Dynamics: A Call for Medical Education Reform. Neurosurgery 21 35522666
2019 CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by repressing PI3K/AKT signaling pathway via interaction with Integrin β1 and Merlin. International journal of biological sciences 21 31523184
2014 Heterozygous deletion of CHL1 gene: detailed array-CGH and clinical characterization of a new case and review of the literature. European journal of medical genetics 21 25451713
2011 Living in a box or call of the wild? Revisiting lifetime inactivity and sarcopenia. Antioxidants & redox signaling 21 21539480
2007 Chl1 and Ctf4 are required for damage-induced recombinations. Biochemical and biophysical research communications 21 17222391
2019 Long noncoding RNA CHL1-AS1 promotes cell proliferation and migration by sponging miR-6076 to regulate CHL1 expression in endometrial cancer. Journal of cellular biochemistry 20 31736153
2017 MicroRNA-Mediated Regulation of ITGB3 and CHL1 Is Implicated in SSRI Action. Frontiers in molecular neuroscience 20 29163031
2015 Interaction between CHL1 and serotonin receptor 2c regulates signal transduction and behavior in mice. Journal of cell science 20 26527397

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