The Sec1 Family: A Novel Family of Proteins Involved in Synaptic Transmission and General Secretion

Authors

  • Naomi Halachmi,

    1. Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel
    Search for more papers by this author
  • Zeev Lev

    Corresponding author
    1. Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel
      Address correspondence and reprint requests to Dr. Z. Lev at Department of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
    Search for more papers by this author

Address correspondence and reprint requests to Dr. Z. Lev at Department of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.

Abstract

Abstract: 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 subcellular 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.

Ancillary