[
International C. elegans Meeting,
1999]
In mammalian cells polypeptide hormones and neurotransmitters are stored in dense cored granules formed directly from the trans Golgi network (TGN) and transported to their site of exocytosis along microtubular pathways. Unlike synaptic vesicles, they cannot be refilled after exocytosis and the granule membrane proteins follow a distinct trafficking route in the cell. The dense cored granule membrane protein phogrin of the insulin-secreting pancreatic b -cell provides a convenient marker of insulin granule movement and biogenesis. It undergoes phosphorylation in response to secretagogues indicating that it may be involved in regulation of granule locomotion or exocytosis. Phogrin is also a major autoantigen in Type I Diabetes patients. The presence of a closely related C. elegans homologue B0244.2 provides an opportunity to study the function of the protein in a species that is tractable both in terms of genetic manipulation and visualization of cell trafficking. The full length cDNA of B0244.2 was sequenced and encodes a putative 86.7 kD transmembrane protein that is 55% identical in its C-terminal domain to rat pancreatic islet phogrin. This region is homologous (25-40% identity) to the larger family of protein tyrosine phosphatases (PTP) though neither B0244.2 nor phogrin appear enzymatically active. The tissue distribution of B0244.2 in C. elegans was examined by microinjection of a GFP construct driven by either a 2.4 or 7.6 kb upstream promoter of the C. elegans gene. The fluorescence tag decorated a series of 20-30 neuronal cell bodies in the head, tail and vulva of the worms with a lesser signal extending into axonal structures. The neuronal localization of B0244.2 in C. elegans parallels the neuroendocrine distribution of phogrin in mammals and indicates that the molecule has great potential for future cell biological studies of the function of these molecules in neurotransmission and disease processes.