title: Cyclin-dependent kinase 5-dependent phosphorylation of Pctaire1 regulates dendrite development.
abstract: Pctaire1, a Cdk-related protein kinase, is prominently expressed in terminally differentiated tissues, including the brain and the testis. We have previously shown that Pctaire1 regulates neurotransmitter release through phosphorylation of NSF, and its kinase activity is regulated by the Cdk5-dependent phosphorylation at Serine-95 (Ser95). Nonetheless, the functional roles of Pctaire1 in neurons during development remained poorly understood. In this study, we found that Pctaire1 is expressed along neurites and is concentrated at the growth cones of early differentiating hippocampal neurons. Upon maturation of these neurons, Pctiare1 is expressed as puncta and co-localized with synaptic marker in dendrites. Phosphorylation of Pctaire1 at Ser95 increases upon neuronal differentiation, concurrent with the elevation in Cdk5 activity. Knockdown of Pctaire1 abolishes dendrite development, and more importantly, expression of Ser95 phosphorylation-deficient mutant of Pctaire1 also reduces dendrite complexity, suggesting that Cdk5 regulates Pctaire1 functions in differentiating neurons. Together, our findings demonstrate that Cdk5-dependent phosphorylation of Pctaire1 at Ser95 plays an important role in dendrite development.
authors.affiliation: Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
authors.forename: W-Y
authors.initials: WY
authors.lastname: Fu
authors.forename: K
authors.initials: K
authors.lastname: Cheng
authors.forename: A K Y
authors.initials: AK
authors.lastname: Fu
authors.forename: N Y
authors.initials: NY
authors.lastname: Ip
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; C089463:PCTAIRE-1 protein kinase