Calpain (calcium-dependent protease; EC 3.4.22.17 ) is an intracellular protease that requires
calcium for its catalytic activity. Two isozymes (CANP1 and CANP2), with different calcium
requirements, have been identified. Both are heterodimers composed of L (large, catalytic, 80
kD) and S (small, regulatory, 30 kD) subunits.
NCBI Summary:
The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq]
General function
Hydrolase, Peptidase/Protease
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Cumulus expansion
Comment
EGF-Like Factors Induce Expansion of the Cumulus Cell-Oocyte Complexes by Activating Calpain-Mediated Cell Movement. Kawashima I et al. Cumulus cell-oocyte complex (COC) expansion is obligatory for LH-induced ovulation and is initiated by LH induction of the epidermal growth factor (EGF)-like factors that mediate the synthesis of the hyaluronan-rich matrix and hyaluronan-stabilizing factors. COC expansion also involves the movement of cumulus cells within the matrix by mechanisms that have not been characterized. We document herein that two proteases, calpain 2 and to a lesser extent calpain 1, are expressed in cumulus cells and that the proteolytic activity of these enzymes is rapidly and significantly increased in COC isolated from human chorionic gonadotropin-induced ovulatory follicles in vivo. Stimulation of calpain activity was associated with proteolytic degradation of paxillin and talin (two components of focal adhesion complexes), cell detachment, and the formation of cell surface bleb-like protrusions. Injection of a calpain inhibitor in vivo reduced 1) human chorionic gonadotropin-stimulated calpain enzyme activity, 2) cell detachment, 3) membrane protrusion formation, and 4) COC expansion by mechanisms that did not alter Has2 expression. During EGF-like factor induction of COC expansion in culture, calpain activity was increased by ERK1/2 and intracellular Ca(2+) signaling pathways. Inhibition of calpain activity in cultured COC blocked cumulus cell detachment, protrusion formation, and the vigorous movement of cumulus cells. As a consequence, COC expansion was impaired. Collectively, these results show that two highly coordinated processes control COC expansion. One process involves the synthesis of the hyaluronan matrix, and the other mediates cumulus cell detachment and movement. The latter are controlled by calpain activation downstream of the EGF receptor activation of the Ca(2+) pathway and ERK1/2 pathways.
Expression regulated by
LH
Comment
Ovarian localization
Oocyte, Cumulus
Comment
Expression and immunolocalization of the calpain-calpastatin system in the human oocyte Ben-Aharon I, et al .
OBJECTIVE: To investigate the expression of the calpain-calpastatin system in the human oocyte. DESIGN: The expression of the calpain-calpastatin system was determined by immunohistochemistry and immunoblot analysis. SETTING: Academic research laboratory. PATIENT(S): Twenty Israeli women who underwent IVF for fertility problems. INTERVENTION(S): Oocytes that had no pronuclei 24 hours after insemination by either conventional IVF or intracytoplasmic sperm injection were retrieved for the study. MAIN OUTCOME MEASURE(S): Analysis of calpain isoforms (m, mu) and calpastatin distribution within the human oocyte. RESULT(S): Western blot analysis confirmed the expression of calpain and calpastatin. Immunohistochemistry of fixed, permeabilized oocytes exhibited localization of both calpains to the cortical region of the oocyte, as well as the cytosol. Calpastatin seemed to be distributed throughout the cytosol, with a marked accumulation in the cell membrane. We have demonstrated a negative correlation between the occurrence of cortical granule exocytosis and the stability of the metaphase plate. CONCLUSION(S): A complete calpain-calpastatin system is expressed in the human oocyte and might play a role in the various calcium-mediated processes occurring during activation of human oocytes.