Open AccessThe cell adhesion molecule CHL1 interacts with patched-1 to regulate apoptosis during postnatal cerebellar development
Author(s) -
Jelena Katić,
Gabriele Loers,
Jelena Tošić,
Melitta Schachner,
Ralf Kleene
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.194563
Subject(s) - biology , microbiology and biotechnology , cell adhesion molecule , cell adhesion , apoptosis , patched , adhesion , cerebellum , cell , neuroscience , genetics , signal transduction , hedgehog signaling pathway , chemistry , organic chemistry
The immunoglobulin superfamily adhesion molecule close homolog of L1 (CHL1) plays important roles during nervous system development. Here, we identified the hedgehog receptor patched-1 (PTCH1) as novel CHL1 binding partner and showed that CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain. Co-localization and -immunoprecipitation of CHL1 with PTCH1 suggest an association of CHL1 with this major component of the hedgehog signaling pathway. The trans-interaction of CHL1 with PTCH1 promotes neuronal survival in cultures of dissociated cerebellar granule cells and of organotypic cerebellar slices. An inhibitor of the PTCH1-regulated hedgehog signal transducer smoothened (SMO) and inhibitors of RhoA and Rho-associated kinase (ROCK) prevent CHL1-dependent survival of cultured cerebellar granule cells and survival of cerebellar granule and Purkinje cells in organotypic cultures. In histological sections from 10- and 14-day-old CHL1-deficient mice enhanced apoptosis of granule, but not Purkinje cells was observed. The results of the present study indicate that CHL1 triggers PTCH1-, SMO-, RhoA- and ROCK-dependent signal transduction pathways to promote neuronal survival after cessation of the major morphogenetic events in mouse cerebellar development.