| First Author | Katic J | Year | 2017 |
| Journal | J Cell Sci | Volume | 130 |
| Issue | 15 | Pages | 2606-2619 |
| PubMed ID | 28630165 | Mgi Jnum | J:250545 |
| Mgi Id | MGI:5924304 | Doi | 10.1242/jcs.194563 |
| Citation | Katic J, et al. (2017) The cell adhesion molecule CHL1 interacts with patched-1 to regulate apoptosis during postnatal cerebellar development. J Cell Sci 130(15):2606-2619 |
| abstractText | 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 a novel CHL1-binding protein and showed that CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain. Colocalization and co-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) 1 and 2 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 during mouse cerebellar development. |
