Disease relevance of CHL1

• Additional characterization of DMF10.167.4 revealed that this antibody was able to induce apoptosis and/or block cellular proliferation when cultured in vitro with the human Jurkat T lymphoma, CHL-1 melanoma, and SBC-3 small cell lung carcinoma lines [1].

Psychiatry related information on CHL1

• Here we report that mice constitutively deficient for CHL1 display reduced reactivity to environmental stimuli and reduced expression of social behaviors, whereas cognitive, motor and olfactory functions are normal [2].
• Investigation of MR patients with 3p aberrations led to the identification of the translocation breakpoint in intron five of the neural Cell Adhesion L1-Like (CALL or CHL1) gene in a man with non-specific mental retardation and 46,Y, t(X;3)(p22.1;p26.3) [3].
• Our data show that the permanent absence of CHL1 results in misguided axonal projections and aberrant axonal connectivity and alters the exploratory behavior in novel environments, suggesting deficits in information processing in CHL1-deficient mice [4].

High impact information on CHL1

• The Adhesion Molecule CHL1 Regulates Uncoating of Clathrin-Coated Synaptic Vesicles [5].
• Generation of new clathrin-coated synaptic vesicles in an activity-dependent manner is inhibited when the CHL1/Hsc70 complex is disrupted, resulting in impaired uptake and release of FM dyes in synaptic boutons [5].
• CHL1 accumulates in presynaptic membranes and, in response to synapse activation, is targeted to synaptic vesicles by endocytosis [5].
• The close homolog of L1 (CHL1), a recently identified member of the L1 family of cell adhesion molecules, is expressed by neurons and glia in the central nervous system and by Schwann cells in the peripheral nervous system in a pattern overlapping, but distinct from, the other members of the L1 family [4].
• However, this antibody was able to prevent murine E710.2.3 lymphoma, human CHL-1 melanoma, and SBC-3 small cell lung carcinoma lines from establishing tumors in vivo and blocked progression of established CHL-1 and SBC-3 tumors in vivo [1].

Biological context of CHL1

• An association between this CHL1 gene polymorphism and schizophrenia supports the notion that cell adhesion molecules are involved in the etiology of schizophrenia [6].
• We screened for mutations in the coding region of the close homologue to L1 gene (CHL1), which is located on human chromosome 3p26, in 24 Japanese patients with schizophrenia [6].
• Basal synaptic transmission and plasticity in seven major excitatory connections in the hippocampus were analyzed to test whether dysfunctions in this brain region, which controls complex behaviors, correlate with the behavioral alterations of CHL1 deficient mice [2].
• These results support a role for CHL1 in integrin-dependent cell migration that may be physiologically important in regulating cell migration in nerve regeneration and cortical development [7].
• In humans, loss or alteration of the CHL1/CALL gene may contribute to mental impairment associated with the 3p-syndrome, caused by distal deletions of the short (p) arm of chromosome 3, and schizophrenia [8].

Anatomical context of CHL1

• Taking in consideration the function of these synapses in processing information from cortical areas, we hypothesize that constitutive ablation of CHL1 leads to reduced capability to react to external stimuli due to dysfunctions in the dentate gyrus [2].
• We found that basal synaptic transmission in lateral and medial perforant path projections to the dentate gyrus is elevated in CHL1-deficient mice [2].
• To identify the molecules which are involved in EVT differentiation, we have raised a monoclonal antibody (mAb) designated CHL1, by immunizing a mouse against human chorion laeve which is composed of EVT [9].
• Close homolog of L1 (CHL1) is a member of the L1 family of cell adhesion molecules expressed by subpopulations of neurons and glia in the central and peripheral nervous system [7].
• Mice deficient for the Close Homologue of L1 (CHL1) show aberrant connectivity of hippocampal mossy fibers and olfactory sensory axons, suggesting participation of CHL1 in the establishment of neuronal networks [8].

Associations of CHL1 with chemical compounds

• A positive association has been reported between a missense polymorphism in CHL1 gene and schizophrenia in the Japanese population [Sakurai, K., Migita, O., Toru, M., Arinami, T., 2002. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol. Psychiatry 7, 412-415] [10].
• Deletion mutants of CHL1 or CTF4, which are required for sister chromatid cohesion, showed higher sensitivity to the DNA damaging agents methyl methanesulfonate (MMS), hydroxyurea (HU), phleomycin, and camptothecin, similar to the phenotype of mutants of RAD52, which is essential for recombination repair [11].
• Mutation of Ser474 to Ala blocks CS addition in Chinese hamster ovary and COS-7 cells but not CHL-1 cells which add CS to Ser472 and Ser474 [12].
• The levels of Chl1 and Ctf4 associated with chromatin increased considerably after exposure of the cells to MMS and phleomycin [11].
• The antibiotic antagonism demonstrated in these studies could be reduced by injecting CHL 1 hour after PCN instead of 1 hour before PCN [13].

Other interactions of CHL1

• This study describes a novel function for CHL1 in potentiating integrin-dependent cell migration toward extracellular matrix proteins [7].
• We suggest that 3p- syndrome associated features are primarily caused by loss of CNTN4 and CRBN, with loss of CHL1 probably having an additional detrimental effect on the cognitive functioning of the present patient [14].

References