rSec6 and rSec8, mammalian homologs of yeast proteins essential for secretion.
Many of the molecules necessary for neurotransmission are homologous to proteins involved in the Golgi-to-plasma membrane stage of the yeast secretory pathway. Of 15 genes known to be essential for the later stages of vesicle trafficking in yeast, 7 have no identified mammalian homologs. These include the yeast SEC6, SEC8, and SEC15 genes, whose products are constituents of a 19.5S particle that interacts with the GTP-binding protein Sec4p. Here we report the sequences of rSec6 and rSec8, rat homologs of Sec6p and Sec8p. The rSec6 cDNA is predicted to encode an 87-kDa protein with 22% amino acid identity to Sec6p, and the rSec8 cDNA is predicted to encode a 110-kDa protein which is 20% identical to Sec8p. Northern blot analysis indicates that rSec6 and rSec8 are expressed in similar tissues. Immunodetection reveals that rSec8 is part of a soluble 17S particle in brain. COS cell cotransfection studies demonstrate that rSec8 colocalizes with the GTP-binding protein Rab3a and syntaxin 1a, two proteins involved in synaptic vesicle docking and fusion at the presynaptic terminal. These data suggest that rSec8 is a component of a high molecular weight complex which may participate in the regulation of vesicle docking and fusion in brain.
Ting
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AE
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University Medical Center, CA 94305-5428, USA.
Hazuka
C D
CD
Hsu
S C
SC
Kirk
M D
MD
Bean
A J
AJ
Scheller
R H
RH
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001483:Base Sequence; D001692:Biological Transport; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain; D002352:Carrier Proteins; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000378:metabolism; D015723:Gene Library; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission; D050827:Syntaxin 1; D015003:Yeasts / Q000235:genetics; D020692:rab3 GTP-Binding Proteins
D000954:Antigens, Surface; D002352:Carrier Proteins; C096102:Exoc3 protein, rat; C076326:Exoc4 protein, rat; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins