The non-lysosomal, calcium-dependent proteolytic system of mammalian cells.
The intracellular calcium-dependent proteases (calpains) and their endogenous protein inhibitor (calpastatin) are present in many different mammalian cells. There is emerging evidence for their importance in the turnover of membrane-associated proteins. Accordingly, it is important to understand how these proteinases and their inhibitor interact within cells, in particular at membranes. Bovine myocardial calpastatin appears to be associated in part with intracellular membranes, where it may effectively block the activity of calpain II on membrane-associated proteins. Immuno-electron microscopic studies suggest that canine myocardial calpain and calpastatin are associated with a number of membranous organelles. During canine myocardial autolysis, the amount of calpain at various organelles decreased, but the amount of calpastatin decreased to an even greater extent. Thus there may be a high calpain to calpastatin balance during heart ischemia at these sites. Calpain II aggregation may contribute to localization of the proteinase at sites of high calcium concentration within cells. A model is presented for interaction of calpain II and calpastatin at cellular membranes in the presence of calcium.
Mellgren
R L
RL
Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Renno
W M
WM
Lane
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D001329:Autolysis; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D004285:Dogs; D004912:Erythrocytes / Q000201:enzymology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009206:Myocardium / Q000201:enzymology*; D010449:Peptide Mapping; D010743:Phospholipids / Q000502:physiology; D011485:Protein Binding; D012508:Sarcolemma / Q000201:enzymology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology
D002135:Calcium-Binding Proteins; D010743:Phospholipids; C033668:calpastatin; D002154:Calpain