Reduction of Crk and CrkL expression blocks reelin-induced dendritogenesis.
The reelin signaling pathway regulates nervous system function after birth, in addition to its role in regulating neuronal positioning during embryogenesis. The receptor-dependent, reelin-induced tyrosine phosphorylation of the Dab1 docking protein is an established prerequisite for biological responses to this ligand. Here we show that the inactivation of a conditional Dab1 allele reduces process complexity in correctly positioned neurons in the CA1 region of the mouse hippocampus after birth. Reelin stimulation of cultured hippocampal neurons enhances dendritogenesis by approximately twofold and in a manner dependent on Src family kinases. This enhancement is blocked by reducing expression of Crk family proteins, adaptor molecules that interact with Dab1 in a tyrosine phosphorylation-dependent manner. Retrovirally expressed inhibitory RNAs used to reduce Crk and CrkL expression did not block BDNF-enhanced dendritogenesis or influence axonogenesis. Together, this demonstrates that the Crk family proteins are important downstream components of the reelin signaling pathway in the regulation of postnatal hippocampal dendritogenesis.
Matsuki
Tohru
T
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Pramatarova
Albéna
A
Howell
Brian W
BW
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D015536:Down-Regulation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D034741:RNA, Small Interfering; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D016622:Silver Staining; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D015816:Cell Adhesion Molecules, Neuronal; C476798:Crk protein, mouse; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D050737:Proto-Oncogene Proteins c-crk; D034741:RNA, Small Interfering; D000091042:Reelin Protein; D019061:src-Family Kinases; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases