Calpain inhibitor inhibits secretory granule maturation and secretion of GH.
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.
Ohkawa
K
K
Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
Takada
K
K
Asakura
T
T
Hashizume
Y
Y
Okawa
Y
Y
Tashiro
K
K
Ueda
J
J
Itoh
Y
Y
Hibi
N
N
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002966:Clathrin / Q000187:drug effects / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D006023:Glycoproteins; D008565:Membrane Proteins; C400241:benzyloxycarbonylleucyl-leucine aldehyde; C039304:calpain inhibitors; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D002154:Calpain