Table 2 Functional diversity of calpains
From: The calpains: modular designs and functional diversity
Examples of proposed calpain function(s) | Model systems providing key supporting evidence | Calpain implicated (possible substrates) | Selected references |
|---|---|---|---|
Participant in signaling pathways | |||
EGF-EGFR-induced motility | Mouse NR6 fibroblasts and derivatives, Hs68 (human neonatal foreskin fibroblasts) | Calpain-2 (?) | [7,45,47] |
Integrin receptor-linked motility | Platelets, bovine aortic endothelial cells, CHO, CHO KI1 and SHI derivative, goldfish fin CAR, and immortalized mouse embryonic fibroblasts deficient in Cpns-1 (capn4-/-) | Calpain-1 leading edge; calpain-2 trailing edge (talin, filamin, spectrin, β-integrin) | [6,48,71] |
Integrin receptor-linked adhesion | Mouse cell line NIH3T3 | Calpain-2 (ezrin) | [72] |
Downstream of VEGF | Pulmonary microvascular endothelial cells | Calpain-2 (?) | [73] |
Responsive to TRPM7 | Flp in T rex 293 derivatives | Calpain-2 (talin) | [74] |
Adaptation to alkaline environment | Emericella (Aspergillus) nidulans, Candida albicans, Saccharomyces cerevisiae | PalB or Rim13/Clp1 | [41,75] |
Downstream of endothelin-1 in development | Mice, HeLa cells, NIH3T3 or HEK293 | Calpain-6 (a non-catalytic form; binds to and stabilizes microtubules) | [18] |
Shear stress induced motility | Human umbilical vein endothelial cells | Calpain-2 (pp125FAK, ezrin) | [76] |
Cellular transformation and tumorigenesis | |||
v-src-transformed cells | HT1080 human fibrosarcoma, H1299 non-small cell lung carcinoma | Implied calpains 1 and 2 (FAK, paxillin) | [48,77] |
capn9 gene disruption | Mouse cell line NIH3T3 | Calpain-9 | [32] |
Necrosis and/or apoptosis | |||
Toxicant induced damage to liver or kidney | Rat/mouse exposure to selected toxicants | Extracellular calpain (fibronectin) | [51-53] |
Neuronal cell death | C. elegans, cell culture (for example, SH-SY5Y), primary cells | Isoforms not defined Bax, Bid, AIF, caspase) | [55-57] |
Cerebellar granule cell survival | Rat, primary cells | Nuclear localized calpain-2 | [78] |
Apoptosis of pancreatic islet cells | Islets (human, mouse) MIN6 β cells exposed to ryanodine or palmitate and low glucose | Calpain-10 | [36,38,39] |
Autophagy/apoptosis switch | Neutrophil, Jurkat, USO2, cpns1-/- MEF | Isoform not defined (Atg5) | [60,61] |
StrepB-induced apoptosis | Macrophage | Calpain-2 (Bax, Bid) | [58] |