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Publication : The Sec1 family: a novel family of proteins involved in synaptic transmission and general secretion.

First Author  Halachmi N Year  1996
Journal  J Neurochem Volume  66
Issue  3 Pages  889-97
PubMed ID  8769846 Mgi Jnum  J:31434
Mgi Id  MGI:78942 Doi  10.1046/j.1471-4159.1996.66030889.x
Citation  Halachmi N, et al. (1996) The Sec1 family: a novel family of proteins involved in synaptic transmission and general secretion. J Neurochem 66(3):889-97
abstractText  The Sec1 family, a novel family of proteins involved in synaptic transmission and general secretion, is described. To date, 14 members of this family have been identified: four yeast proteins, Sec1, Sly1, Slp1/Vps33, and Vps45/Stt10; three nematode proteins, Unc-18 and the homologues of Sly1 and Slp1; the Drosophila Rop; and six mammalian proteins, the rat Munc-18/n-Sec1/rbSec1A and rbSec1B, the mouse Munc-18b/muSec1 and Munc-18c, and the bovine Munc-18 and mSec1. The mammalian proteins share 44-63% sequence identity with the nematode Unc-18 and Drosophila Rop proteins and 20-29% with the yeast proteins and their nematode homologues. The Sec1 proteins are mostly hydrophilic and lack a transmembrane domain. Nevertheless, Sec1 proteins are found as membrane-bound proteins. Some of them are also found as soluble, cytoplasmic proteins. Binding of the rat brain Sec1 to the presynaptic membrane may be due to strong interaction with syntaxin, an integral component of this membrane. The rat brain Sec1 is also bound to Cdk5, a neural cyclin-dependent kinase. The Sec1 proteins play a positive role in exocytosis. Loss of function mutations in SEC1, SLY1, or SLP1 result in blocking of protein transport between distinct yeast sub-cellular compartments. Inactivation of unc-18 and rop results in inhibition of neurotransmitter release and, in the case of rop, inhibition of general secretion as well. In addition, studies of Rop and n-Sec1 indicate that they also play a negative role in synaptic transmission, mediated by their interaction with syntaxin. A working model addressing the dual regulative role of the Sec1 proteins in secretion is presented.
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