Calpain inhibitor inhibits secretory granule maturation and secretion of GH

• Published in: Neuroreport Vol. 11; no. 18; p. 4007
• Main Authors: Ohkawa, K, Takada, K, Asakura, T, Hashizume, Y, Okawa, Y, Tashiro, K, Ueda, J, Itoh, Y, Hibi, N
• Format: Journal Article
• Language: English
• Published: England 18.12.2000
• Subjects: Adaptor Protein Complex alpha Subunits; Adaptor Proteins, Vesicular Transport; Animals; Calpain - antagonists & inhibitors; Calpain - metabolism; Clathrin - drug effects; Clathrin - metabolism; Cysteine Proteinase Inhibitors - pharmacology; Dipeptides - pharmacology; Dose-Response Relationship, Drug; Glycoproteins - pharmacology; Golgi Apparatus - drug effects; Golgi Apparatus - metabolism; Growth Hormone - metabolism; Growth Hormone-Releasing Hormone - pharmacology; Membrane Proteins - drug effects; Membrane Proteins - metabolism; Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - metabolism; Pituitary Gland, Anterior - ultrastructure; Rats; Secretory Vesicles - drug effects; Secretory Vesicles - metabolism; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism
• ISSN: 0959-4965
• DOI: 10.1097/00001756-200012180-00021

Clathrin- and AP-1-coated buds are present on immature secretory granules of endocrine cells that mature into clathrin-uncoated granules. The mechanism of clathrin and adaptor protein uncoating has remained obscure. Benzyloxycarbonyl-L-leucyl-L-leucinal (ZLLal), a calpain inhibitor, reduced growth hormone (GH) secretion with intracellular accumulation, in a GH-secreting rat pituitary tumor cell. Pulse and chase demonstrated that ZLLal retarded the turnover of clathrin (Clt.H) and adaptins. ZLLal-treatment co-immunoprecipitated the increased amounts of GH with Clt.H and adaptins compared to control cells, suggesting the intracellular accumulation of immature secretory granules. Clt.H and adaptins were limited-proteolyzed by m-calpain in vitro, indicating that calpain may be involved partly in the maturation of secretory granules in endocrine cells via the process of clathrin uncoating.