Function: By quantitative RT-PCR, Ueyama et al. (1998) found that expression of calpain-1 and calpain-2 mRNA was significantly increased in muscle biopsy samples derived from 5 men with progressive muscular dystrophy (e.g., DMD; OMIM:310200) and 2 men and 3 women with amyotrophic lateral sclerosis (ALS; OMIM:105400) compared with controls.

Function: Morford et al. (2002) found that calpain-2, but not calpain-1, associated with membrane lipid rafts on human peripheral blood T cells and Jurkat T cells. Membrane raft-associated calpain activity in human T cells was enhanced with exogenous calcium. Calpain cleaved the cytoskeletal-associated protein talin (TLN1; OMIM:186745) during the first 30 minutes after cell stimulation. Morford et al. (2002) hypothesized that lipid raft-associated calpain-2 could function early in T-cell receptor signaling to facilitate immune synapse formation through cytoskeletal remodeling mechanisms.

Function: Using confocal microscopy and isopycnic density centrifugation, Hood et al. (2003) found that calpain-1, calpain-2, the small regulatory calpain subunit, and calpastatin (CAST; OMIM:114090) associated with the endoplasmic reticulum and Golgi apparatus of human fibroblasts and glioblastoma cells. The association between these proteins and the endoplasmic reticulum and Golgi apparatus increased in the glioblastoma cell line following laminin (see LAMA1; OMIM:150320) stimulation. Calpain-2 also colocalized with inositol 4,5-bisphosphate and with membrane lipid rafts.

Function: Adamec et al. (2002) investigated calpain-2 activation in a broad range of neurodegenerative diseases using immunofluorescence imaging. Activated calpain-2 was detected in all neurodegenerative diseases examined, including Alzheimer disease (AD; OMIM:104300), Down syndrome (OMIM:190685), and Pick disease (OMIM:172700), with the possible exception of frontotemporal dementia with inclusions (see OMIM:600274). Activated calpain-2 was detected in different cell types and colocalized with different pathologic structures. In neurons and glial cells, calpain-2 primarily colocalized with hyperphosphorylated tau protein (MAPT; OMIM:157140). In brains with AD neurofibrillary changes, colocalization of calpain-2 with phosphorylated tau was most extensive at transentorhinal stages of neurofibrillary degeneration rather than at later limbic stages. Aggregates of different proteins, such as huntingtin (HD; OMIM:143100) and alpha-synuclein (SNCA; OMIM:163890), were negative for activated calpain-2, indicating that the presence of pathologic inclusions was not by itself the stimulus responsible for calpain-2 activation.