Interplay in neural functions of cell adhesion molecule close homolog of L1 (CHL1) and Programmed Cell Death 6 (PDCD6)

• Published in: FASEB bioAdvances Vol. 4; no. 1; pp. 43 - 59
• Main Authors: Loers, Gabriele, Theis, Thomas, Baixia Hao, Helen, Kleene, Ralf, Arsha, Sanjana, Samuel, Nina, Arsha, Neha, Young, Wise, Schachner, Melitta
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-01-2022; John Wiley and Sons Inc; Wiley
• Subjects: Antibodies; Apoptosis; Astrocytes; Axonogenesis; Brain; Ca2; Cell adhesion & migration; cell adhesion molecule; Cell adhesion molecules; Cell death; Cell surface; Cerebellum; CHL1; CHL1 protein; Chromatography; Cloning; Extracellular matrix; Granule cells; Homogenization; Immunoprecipitation; Kinases; Mass spectrometry; Nervous system; PDCD6; Pons; Proteins; Reagents; Regeneration; Scientific imaging; Signal transduction; Synaptic plasticity; Trauma; cell adhesion molecule; nervous system; CHL1; Ca2; PDCD6
• ISSN: 2573-9832; 2573-9832
• DOI: 10.1096/fba.2021-00027

Close homolog of L1 (CHL1) is a cell adhesion molecule of the immunoglobulin superfamily. It promotes neuritogenesis and survival of neurons in vitro. In vivo, CHL1 promotes nervous system development, regeneration after trauma, and synaptic function and plasticity. We identified programmed cell death 6 (PDCD6) as a novel binding partner of the CHL1 intracellular domain (CHL1‐ICD). Co‐immunoprecipitation, pull‐down assay with CHL1‐ICD, and proximity ligation in cerebellum and pons of 3‐day‐old and 6‐month‐old mice, as well as in cultured cerebellar granule neurons and cortical astrocytes indicate an association between PDCD6 and CHL1. The Ca2+‐chelator BAPTA‐AM inhibited the association between CHL1 and PDCD6. The treatment of cerebellar granule neurons with a cell‐penetrating peptide comprising the cell surface proximal 30 N‐terminal amino acids of CHL1‐ICD inhibited the association between CHL1 and PDCD6 and PDCD6‐ and CHL1‐triggered neuronal survival. These results suggest that PDCD6 contributes to CHL1 functions in the nervous system.