Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components.
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.
Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, California 94305, USA.
Chan-Yen
CY
Ou
Vivian Y
VY
Poon
Celine I
CI
Maeder
Shigeki
S
Watanabe
Emily K
EK
Lehrman
Amy K Y
AK
Fu
Mikyoung
M
Park
Wing-Yu
WY
Fu
Erik M
EM
Jorgensen
Nancy Y
NY
Ip
Kang
K
Shen
D000818:Animals; D001369:Axons; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D009474:Neurons; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D016213:Cyclins; D018844:Cyclin-Dependent Kinases; D016547:Kinesins