NOC2, A PUTATIVE ZINC-FINGER PROTEIN INVOLVED IN EXOCYTOSIS IN ENDOCRINE-CELLS

We have cloned a cDNA encoding a novel protein of 302 amino acids (des ignated Noc2, no C2 domain) that has 40.7% amino acid identity with an d 77.9% similarity to the N-terminal region of rabphilin-3A, a target molecule of Rab3A However, unlike rabphilin-3A, Noc2 lacks two C2 doma ins that are thought to interact with Ca2+ and phospholipids. Noc2 is expressed predominantly in endocrine tissues and hormone-secreting cel l lines and at very low levels in brain. Immunoblot analysis of subcel lular fractions of the insulin-secreting cell line MING and immunocyto chemistry reveal that Noc2 is a 38-kDa protein present in the cytoplas m. Overexpression of Noc2 in PC12 cells cotransfected with growth horm one enhances high K+-induced growth hormone secretion. Screening a mou se embryonic cDNA Library with the yeast two-hybrid system shows that Noc2 interacts with the LIM domain-containing protein zyxin, a compone nt of the cytoskeleton, and this interaction is further confirmed by t he coimmunoprecipitation experiment. Accordingly, Noc2 is probably inv olved in regulated exocytosis in endocrine cells by interacting with t he cytoskeleton.