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 tissues 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 residues 609 to 617) revealed several additional posttranslational products. Peptides of apparent molecular sizes of 20, 18, and 10 kDa were prominent in nerve tissues and the hypophysis but absent in the adrenal medulla, and their relative abundance varied in distinct regions of the CNS. In PC12 cells VGF was proteolytically processed only after nerve growth factor treatment, and primary cultures of rat cerebellar granule cells accumulated the low-molecular-weight forms of VGF during in vitro maturation. In these cells the specific cleavages of VGF occurred in a postendoplasmic reticulum compartment; the processed forms were enriched in the secretory vesicles and were preferentially secreted upon cell membrane depolarization. Distinct differential distribution in the CNS and in vitro release of such posttranslational products indicate that these species may represent biologically relevant forms of VGF that play a role in neuronal communication.
Trani
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E
Departimento di Medicina Sperimentale e Scienze Biochimiche, Università di Tor Vergata, Roma, Italy.
Ciotti
T
T
Rinaldi
A M
AM
Canu
N
N
Ferri
G L
GL
Levi
A
A
Possenti
R
R
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D000818:Animals; D020126:Brefeldin A; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004702:Endocrine Glands / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D003517:Cyclopentanes; D009414:Nerve Growth Factors; D009479:Neuropeptides; D011500:Protein Synthesis Inhibitors; D011506:Proteins; C512697:Vgf protein, mouse; C062040:Vgf protein, rat; D020126:Brefeldin A; D010447:Peptide Hydrolases