Regulation of SNAREs by Tomosyn and ROCK: Implication in Extension and Retraction of Neurites

• Published in: The Journal of cell biology Vol. 166; no. 1; pp. 17 - 25
• Main Authors: Sakisaka, Toshiaki, Baba, Takeshi, Tanaka, Shintaro, Izumi, Genkichi, Yasumi, Masato, Takai, Yoshimi
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05.07.2004; The Rockefeller University Press
• Subjects: Animals; Antigens, Surface - metabolism; Axons; Biological Transport; Carrier Proteins - physiology; Cell Division; Cell Line, Tumor; Cell Membrane - metabolism; Cell membranes; Cell-Free System; Cells; Cultured cells; Genetic Vectors; Growth cones; Hippocampus - metabolism; Insecta; Intracellular Signaling Peptides and Proteins; Membrane Glycoproteins - metabolism; Membrane Proteins - biosynthesis; Membrane Proteins - metabolism; Membranes; Microscopy, Confocal; Models, Biological; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Neurites; Neurites - metabolism; Neurons; Neurons - metabolism; PC12 cells; Phosphorylation; Plasmids; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - physiology; Proteins; R-SNARE Proteins; Rats; rho-Associated Kinases; RNA Interference; SNARE Proteins; Syntaxin 1; Time Factors; Transfection; Vesicular Transport Proteins; Viral Envelope Proteins - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200405002

Extension of neurites requires the SNARE-dependent fusion of plasmalemmal precursor vesicles with the plasma membrane of growth cones. Here, we show that tomosyn localizes at the palm of growth cones and inhibits the fusion of the vesicles there, thus promoting transport of the vesicles to the plasma membrane of the leading edges of growth cones. Tomosyn localizes because ROCK activated by Rho small G protein phosphorylates syntaxin-1, which increases the affinity of syntaxin-1 for tomosyn and forms a stable complex with tomosyn, resulting in inhibition of the formation of the SNARE complex. In retraction of neurites, tomosyn localizes all over the edges of the neurites and inhibits fusion of the vesicles with the plasma membrane. Thus, tomosyn demarcates the plasma membrane by binding to syntaxin-1 phosphorylated by ROCK, and thereby regulates extension and retraction of neurites.