TISSUE-SPECIFIC PROCESSING OF THE NEUROENDOCRINE PROTEIN VGF

VGF is a neuroendocrine-specific gene product that is up-regulated by nerve growth factor in the PC12 cell line. In rat neuroendocrine tissu es two polypeptides of 90 and 80 kDa were detected by an antiserum to an N-terminal domain of VGF (from residues 4 to 240). In parallel, an antiserum directed against the C-terminal nonapeptide of VGF (from res idues 609 to 617) revealed several additional posttranslational produc ts, Peptides of apparent molecular sizes of 20, 18, and 10 kDa were pr ominent in nerve tissues and the hypophysis but absent in the adrenal medulla, and their relative abundance varied in distinct regions of th e CNS. In PC12 cells VGF was proteolytically processed only after nerv e growth factor treatment, and primary cultures of rat cerebellar gran ule cells accumulated the low-molecular-weight forms of VGF during in vitro maturation, In these cells the specific cleavages of VGF occurre d in a postendoplasmic reticulum compartment; the processed forms were enriched in the secretory vesicles and were preferentially secreted u pon cell membrane depolarization, Distinct differential distribution i n the CNS and in vitro release of such posttranslational products indi cate that these species may represent biologically relevant forms of V GF that play a role in neuronal communication.