The cell adhesion molecule CHL1 interacts with patched-1 to regulate neuritogenesis, neuronal cell migration and apoptosis during postnatal cerebellar development.
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The cell adhesion molecule CHL1 interacts with patched-1 to regulate neuritogenesis, neuronal cell migration and apoptosis during postnatal cerebellar development. / Katic, Jelena; Loers, Gabriele; Tosic, Jelena; Schachner, Melitta; Kleene, Ralf.
In: J CELL SCI, Vol. 130, No. 5, 01.08.2017, p. 2606-2619.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - The cell adhesion molecule CHL1 interacts with patched-1 to regulate neuritogenesis, neuronal cell migration and apoptosis during postnatal cerebellar development.
AU - Katic, Jelena
AU - Loers, Gabriele
AU - Tosic, Jelena
AU - Schachner, Melitta
AU - Kleene, Ralf
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
M3 - SCORING: Journal article
VL - 130
SP - 2606
EP - 2619
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - 5
ER -