J Biol Chem, Vol. 273, Issue 34, 21642-21647, August 21, 1998

Genomic Structure of MUNC18-1 Protein, Which Is Involved in Docking and Fusion of Synaptic Vesicles in Brain

Koshichi Gotoh, Hiroshi Yokota^§, Eriko Kikuya^¶, Toshio Watanabe, and Michio Oishi^¶

From the  Institute of Molecular and Cellular Bioscience, University of Tokyo, Bunkyo, Tokyo 113, Japan, ^§ Daiichi Pharmaceutical Co., Ltd., Edogawa, Tokyo 134, Japan, ^¶ Kazusa DNA Research Institute, Kisarazu, Chiba 292, Japan, and  Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai, Miyagi 980, Japan

MUNC18-1 (n-Sec1) is a brain-specific protein and is known to play a role in neurotransmitter release by mediating docking and fusion of synaptic vesicles to presynaptic membranes. The protein is also implicated in the cellular excretion process of hormones and other biological substances in other mammalian tissues and yeasts. We have studied the structure of mouse munc18-1 gene by sequencing the genomic munc18-1 gene and its 5'-flanking region. munc18-1 gene comprises 19 exons whose size ranges from 50 base pairs (2nd exon) to 1676 base pairs (19th exon) with a total gene size of approximately 56 kilobases. In the 5'-flanking region, there are several transcription factor binding sites such as for HSF2, Lyf-1, and Sp1 but no TATA or CAAT sequences. munc18-1 gene was mapped on mouse chromosome 2 between two anchor markers D2Mit152 and D2Mit242. Transfection experiments employing these and upstream sequences suggest the presence of a sequence(s) that negatively regulates the expression of munc18-1 gene.