Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites.
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.
Sakisaka
Toshiaki
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan.
Baba
Takeshi
T
Tanaka
Shintaro
S
Izumi
Genkichi
G
Yasumi
Masato
M
Takai
Yoshimi
Y
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002474:Cell-Free System; D005822:Genetic Vectors; D006624:Hippocampus / Q000378:metabolism; D007313:Insecta; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017434:Protein Structure, Tertiary; D050683:R-SNARE Proteins; D034622:RNA Interference; D051381:Rats; D050600:SNARE Proteins; D050827:Syntaxin 1; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins / Q000378:metabolism; D054460:rho-Associated Kinases
D000954:Antigens, Surface; D002352:Carrier Proteins; C028391:G protein, vesicular stomatitis virus; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C494213:Stx1a protein, rat; C484769:Stxbp5 protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases