title: Cellular mechanisms underlying the regulation of dendritic development by hepatocyte growth factor.
abstract: Acquisition of a mature dendritic morphology is critical for neural information processing. In particular, hepatocyte growth factor (HGF) controls dendritic arborization during brain development. However, the cellular mechanisms underlying the effects of HGF on dendritic growth remain elusive. Here, we show that HGF increases dendritic length and branching of rat cortical neurons through activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of MAPK by HGF leads to the rapid and transient phosphorylation of cAMP response element-binding protein (CREB), a key step necessary for the control of dendritic development by HGF. In addition to CREB phosphorylation, regulation of dendritic growth by HGF requires the interaction between CREB and CREB-regulated transcription coactivator 1 (CRTC1), as expression of a mutated form of CREB unable to bind CRTC1 completely abolished the effects of HGF on dendritic morphology. Treatment of cortical neurons with HGF in combination with brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that regulates dendritic development via similar mechanisms, showed additive effects on MAPK activation, CREB phosphorylation and dendritic growth. Collectively, these results support the conclusion that regulation of cortical dendritic morphology by HGF is mediated by activation of the MAPK pathway, phosphorylation of CREB and interaction of CREB with CRTC1.
authors: Department of Psychiatry-CHUV, Center for Psychiatric Neuroscience, Prilly-Lausanne, Switzerland.
authors: Charles
authors: C
authors: Finsterwald
authors: Jean-Luc
authors: JL
authors: Martin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C519510:Crtc1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D020928:Mitogen-Activated Protein Kinases