Calpain‐calpastatin and fusion

Glaser, Tova; Kosower, Nechama S.

doi:10.1016/0014-5793(86)81351-5

Cited by 48 publications

(25 citation statements)

References 19 publications

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“…CANPs have been shown to selectively cleave regulatory domains from protein kinase C and calcium-and calmodulin-dependent protein kinase, thereby influencing protein phosphorylation (12)(13)(14)(15). These actions regulate the assembly state and other dynamics of the proteins (15,54) and may underlie the suspected involvement of CANPs in membrane fusion (57,58) and trafficking (59). Abnormalities of the endosomal-lysosomal system are, in fact, an early marker of affected neurons in Alzheimer brain, and these abnormalities may alter APP processing (37,44).…”

Section: Discussionmentioning

confidence: 99%

Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration.

Saitô

Elce

Hamos

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

548

372

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Calcium-activated neutral proteinases (CANPs or calpains) are believed to be key enzymes in intracellular signaling cascades and potential mediators of calciuminduced neuronal degeneration. To investigate their involvement in Alzheimer disease, we identified three isoforms of ,uCANP (calpain I) in human postmortem brain corresponding to an 80-kDa precursor and two autolyticafly activated isoforms (78 and 76 kDa). As an index of changes in the in vivo activity of ,uCANP in Alzheimer disease, the ratio of the 76-kDa

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Section: Discussionmentioning

confidence: 99%

Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration.

Saitô

Elce

Hamos

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

548

372

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“…Cytosol obtained from young individuals was used for the isolation and purification of calpain according to published procedures (2, 16), with units of calpain activity defined as described previously (16,17). Monoclonal antibodies specific to human erythrocyte W-calpain were generated according to established procedures (19).…”

Section: Methodsmentioning

confidence: 99%

“…Partially purified, hemoglobin-free cytosol (Hbfree cytosol) was obtained by loading the cytosol on a DEAE-cellulose column (preequilibrated with Tris-DE) and washing with Tris-DE containing 50 mM NaCl until the eluate was free of hemoglobin. A fraction containing nonhemoglobin proteins, including calpain, was then eluted with Tris-DE containing 150 mM NaCl (15,16). The eluate was dialyzed against 1.0 mM EDTA/1.0 mM EGTA/0.1 mM phenylmethylsulfonyl fluoride (PMSF)/0.5 mM DTT, then lyophilized and resuspended in Tris.…”

Section: Introductionmentioning

confidence: 99%

“…We have shown previously that calpain plays a role in membrane fusion: specifically, that degradation of certain membrane proteins by calpain is a prerequisite for membrane fusion induced by the membrane mobility agent A2C (14)(15)(16). In addition to calpain-induced changes associated with membrane fusion, we have also discovered that the degradation of band 3 protein by p.-calpain is enhanced in erythrocyte membranes of old human individuals (>70 years old) as compared with that in erythrocyte membranes of young ones (20-30 years old) (17).…”

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confidence: 99%

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Calpain (Ca(2+)-dependent thiol protease) in erythrocytes of young and old individuals.

Glaser

Schwarz-Benmeir

Barnoy

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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Limited proteolysis by calpain (Ca2+-activated protease; EC 3.4.22.17) is believed to regulate the function of membrane enzymes and modify the behavior of membrane structural proteins. Calpain is activated by autolysis. The degradation of band 3 protein by #-calpain is known to be enhanced in erythrocyte membranes from human individuals >70 years old (old) as compared with that from individuals 20-30 years old (young). In the present study, monoclonal antibody to IA-calpain was used to study the behavior of calpain in erythrocytes of young and old individuals. Less calpain was found in erythrocyte cytosol and membranes from old than in those from young. Increasing the erythrocyte Ca2+ induced translocation of calpain to the cell membrane and autolysis of the enzyme. Alkylation of erythrocyte thiols also promoted translocation of calpain to the membrane, especially in the presence of Ca2+. When calpain was added to erythrocyte membranes, initial binding was greater and subsequent autolysis faster in old than in young individuals, possibly arising from alterations in cell membranes of old individuals. The enhanced calpain autolysis was accompanied by enhanced degradation of band 3 protein in the old. The results suggest that calpain in old individuals is translocated to the cell membrane and is activated by autolysis, resulting in degradation of certain membrane proteins and loss of calpain. Enhanced calpain-induced membrane proteolysis may play a role in abnormal cell destruction (e.g., shortening the iffe span oferythrocytes in the aged, neuronal degeneration, etc). The erythrocyte membrane provides a convenient model for the study of age-associated alterations in cell membranes and in calpain behavior.Calpain is a neutral Ca2+-dependent thiol protease (EC 3.4.22.17), present in a wide variety of vertebrate cells. Two major isozymes are known, g-calpain and m-calpain, requiring juM and mM Ca2+ for activation, respectively (1-5). The isozyme types and amounts of the protease vary among cells and among species. Calpain is found mainly in the cell cytosol and is usually present in an inactive form. It has been suggested that, in the presence of Ca2+, calpain is activated by limited autolysis, a process that is enhanced by the translocation of calpain to the cell membrane (4-10). Activated calpain causes a limited degradation of certain membrane and cytoskeletal proteins and enzymes. The calpaininduced limited proteolysis may regulate enzyme activities and modulate the behavior of membrane structural proteins (3)(4)(5)(11)(12)(13).The mammalian erythrocyte contains the 1L-calpain isozyme (2). We have shown previously that calpain plays a role in membrane fusion: specifically, that degradation of certain membrane proteins by calpain is a prerequisite for membrane fusion induced by the membrane mobility agent A2C (14-16). In addition to calpain-induced changes associated with membrane fusion, we have also discovered that the degradation of band 3 protein by p.-calpain is enhanced in erythrocyte membranes of o...

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“…This occurs in cells located in the midcortex of the lens, the same zone in which spectrin cleavage is first noted. Calpainmediated cleavage of the submembrane cytoskeleton is essential for successful fusion of erythrocytes (64) or myoblasts (12) and might also be important in the lens.…”

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confidence: 99%

Calpain Expression and Activity during Lens Fiber Cell Differentiation

María

Shi

Kumar

et al. 2009

Journal of Biological Chemistry

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In animal models, the dysregulated activity of calcium-activated proteases, calpains, contributes directly to cataract formation. However, the physiological role of calpains in the healthy lens is not well defined. In this study, we examined the expression pattern of calpains in the mouse lens. Real time PCR and Western blotting data indicated that calpain 1, 2, 3, and 7 were expressed in lens fiber cells. Using controlled lysis, depth-dependent expression profiles for each calpain were obtained. These indicated that, unlike calpain 1, 2, and 7, which were most abundant in cells near the lens surface, calpain 3 expression was strongest in the deep cortical region of the lens. We detected calpain activities in vitro and showed that calpains were active in vivo by microinjecting fluorogenic calpain substrates into cortical fiber cells. To identify endogenous calpain substrates, membrane/cytoskeleton preparations were treated with recombinant calpain, and cleaved products were identified by twodimensional difference electrophoresis/mass spectrometry. Among the calpain substrates identified by this approach was ␣II-spectrin. An antibody that specifically recognized calpaincleaved spectrin was used to demonstrate that spectrin is cleaved in vivo, late in fiber cell differentiation, at or about the time that lens organelles are degraded. The generation of the calpain-specific spectrin cleavage product was not observed in lens tissue from calpain 3-null mice, indicating that calpain 3 is uniquely activated during lens fiber differentiation. Our data suggest a role for calpains in the remodeling of the membrane cytoskeleton that occurs with fiber cell maturation.

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Calpain‐calpastatin and fusion

Cited by 48 publications

References 19 publications

Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration.

Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration.

Calpain (Ca(2+)-dependent thiol protease) in erythrocytes of young and old individuals.

Calpain Expression and Activity during Lens Fiber Cell Differentiation

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