RRC ID 46662
著者 Ou CY, Poon VY, Maeder CI, Watanabe S, Lehrman EK, Fu AK, Park M, Fu WY, Jorgensen EM, Ip NY, Shen K.
タイトル Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components.
ジャーナル Cell
Abstract Polarized trafficking of synaptic proteins to axons and dendrites is crucial to neuronal function. Through forward genetic analysis in C. elegans, we identified a cyclin (CYY-1) and a cyclin-dependent Pctaire kinase (PCT-1) necessary for targeting presynaptic components to the axon. Another cyclin-dependent kinase, CDK-5, and its activator p35, act in parallel to and partially redundantly with the CYY-1/PCT-1 pathway. Synaptic vesicles and active zone proteins mostly mislocalize to dendrites in animals defective for both PCT-1 and CDK-5 pathways. Unlike the kinesin-3 motor, unc-104/Kif1a mutant, cyy-1 cdk-5 double mutants have no reduction in anterogradely moving synaptic vesicle precursors (SVPs) as observed by dynamic imaging. Instead, the number of retrogradely moving SVPs is dramatically increased. Furthermore, this mislocalization defect is suppressed by disrupting the retrograde motor, the cytoplasmic dynein complex. Thus, PCT-1 and CDK-5 pathways direct polarized trafficking of presynaptic components by inhibiting dynein-mediated retrograde transport and setting the balance between anterograde and retrograde motors.
巻・号 141(5)
ページ 846-58
公開日 2010-5-28
DOI 10.1016/j.cell.2010.04.011
PII S0092-8674(10)00385-5
PMID 20510931
PMC PMC3168554
MeSH Animals Axons Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Cyclin-Dependent Kinases / metabolism* Cyclins / metabolism Kinesins / metabolism Neurons Signal Transduction Synapses / metabolism*
IF 38.637
引用数 101
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm2175 tm648 tm1238