TY - JOUR
T1 - Local F-actin network links synapse formation and axon branching
AU - Chia, Poh Hui
AU - Chen, Baoyu
AU - Li, Pengpeng
AU - Rosen, Michael K.
AU - Shen, Kang
N1 - Funding Information:
This work was funded by the Howard Hughes Medical Institute and National Institutes of Health (grant R01 NS048392). P.H. Chia is supported by the Agency for Science, Technology, and Research in Singapore. We thank the International Caenorhabditis Genetic Center and the Japanese National Bioresource Project for strains. We also thank C. Gao for technical assistance.
PY - 2014
Y1 - 2014
N2 - Axonal branching and synapse formation are tightly linked developmental events during the establishment of synaptic circuits. Newly formed synapses promote branch initiation and stability. However, little is known about molecular mechanisms that link these two processes. Here, we show that local assembly of an F-actin cytoskeleton at nascent presynaptic sites initiates both synapse formation and axon branching. We further find that assembly of the F-actin network requires a direct interaction between the synaptic cell adhesion molecule SYG-1 and a key regulator of actin cytoskeleton, the WVE-1/WAVE regulatory complex (WRC). SYG-1 cytoplasmic tail binds to the WRC using a consensus WRC interacting receptor sequence (WIRS). WRC mutants or mutating the SYG-1 WIRS motif leads to loss of local F-actin, synaptic material, and axonal branches. Together, these data suggest that synaptic adhesion molecules, which serve as a necessary component for both synaptogenesis and axonal branch formation, directly regulate subcellular actin cytoskeletal organization.
AB - Axonal branching and synapse formation are tightly linked developmental events during the establishment of synaptic circuits. Newly formed synapses promote branch initiation and stability. However, little is known about molecular mechanisms that link these two processes. Here, we show that local assembly of an F-actin cytoskeleton at nascent presynaptic sites initiates both synapse formation and axon branching. We further find that assembly of the F-actin network requires a direct interaction between the synaptic cell adhesion molecule SYG-1 and a key regulator of actin cytoskeleton, the WVE-1/WAVE regulatory complex (WRC). SYG-1 cytoplasmic tail binds to the WRC using a consensus WRC interacting receptor sequence (WIRS). WRC mutants or mutating the SYG-1 WIRS motif leads to loss of local F-actin, synaptic material, and axonal branches. Together, these data suggest that synaptic adhesion molecules, which serve as a necessary component for both synaptogenesis and axonal branch formation, directly regulate subcellular actin cytoskeletal organization.
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U2 - 10.1016/j.cell.2013.12.009
DO - 10.1016/j.cell.2013.12.009
M3 - Article
C2 - 24439377
AN - SCOPUS:84892742828
SN - 0092-8674
VL - 156
SP - 208
EP - 220
JO - Cell
JF - Cell
IS - 1-2
ER -