MOLECULAR-IDENTIFICATION OF 2 NOVEL MUNC-18 ISOFORMS EXPRESSED IN NONNEURONAL TISSUES

Munc-18, also known as n-Sec1 or rbSec1, is a syntaxin-binding protein thought to play a role in regulating synaptic vesicle exocytosis. Alt hough a gene family of syntaxins has been identified, only a limited s ubset bind to Munc-18. This implicates the existence of other mammalia n Munc-18 homologues that may be involved in a range of vesicle transp ort reactions. The purpose of the present study was to identify other members of the Munc-18 family by cDNA cloning, Three distinct Munc-18 isoforms, Munc-18a, previously identified in neuronal tissue, and two novel isoforms, Munc-18b and Munc-18c, were isolated from a 3T3-L1 adi pocyte cDNA library by screening with a rat brain Munc-18 DNA probe, M unc-18a is identical to Munc-18 and by Northern analysis is expressed predominantly in brain and to a lesser extent in testis and 3T3-L1 cel ls, Munc-18b is 62% identical to Munc-18 at the amino acid level and i s expressed in testis, intestine, kidney, rat adipose tissue, and 3T3- L1 cells, Munc-18c is 51% identical to Munc-18 and is ubiquitously exp ressed. It is likely, based on these findings, that unique Munc-18/syn taxin interactions may play an important role in generating a combinat orial mechanism for the regulation of vesicle transport in mammalian c ells.