High impact information on Capns1

• Homozygous disruption of murine Capn4 eliminated both mu- and m-calpain activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis [1].
• Both mu- and m-calpains are heterodimers, consisting of a distinct large 80-kDa catalytic subunit, encoded by the genes Capn1 and Capn2, and a common small 28-kDa regulatory subunit (Capn4) [1].
• Utilizing transformed fibroblasts from calpain small subunit knock-out (Capns1(-/-)) mouse embryos, we now show that the heterodimeric, typical subclass of calpains is required for calcium-mediated survival after plasma membrane damage caused by scraping a cell monolayer [2].
• The number of focal adhesions was decreased in Capn4(-/-) cells, but the cells had prominent vinculin-containing focal complexes at the cell periphery [3].
• To assess the role of calpain in migration, we used fibroblasts obtained from Capn4(-/-) mouse embryos [3].

Biological context of Capns1

• Accordingly, the enhancement of lysosomal activity and long-lived proteins degradation, normally occurring upon starvation, are also reduced.In Capns1-depleted cells ectopic LC3 accumulates in early endosome-like vesicles that might represent a salvage pathway for protein degradation when autophagy is defective [4].
• We have found that Capns1 depletion is coupled to increasedsensitivitytoincreased sensitivity to apoptosis triggered by a number of autophagy-inducing stimuli in mammalian cells [4].
• Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division [1].

Anatomical context of Capns1

• Capn4(-/-) cells had decreased migration rates and abnormal organization of the actin cytoskeleton with a loss of central stress fibers [3].

Associations of Capns1 with chemical compounds

• Capn4(-/-) MEFs displayed resistance to puromycin, camptothecin, etoposide, hydrogen peroxide, ultraviolet light, and serum starvation, which was consistent with pro-apoptotic roles for calpain [5].

Other interactions of Capns1

• BMY 14802 (1000 microg/kg orally), a sigma receptor antagonist, or cyclosomatostatin (CSS 1 microg/kg intravenously), a somatostatin antagonist, were given five minutes prior to JO 2871 in LPS, E coli-sta, and C difficile toxin treated mice [6].

Analytical, diagnostic and therapeutic context of Capns1

• Therefore we investigated the involvement of calpains in autophagy using MEFs derived from Capns1 knockout mice and Capns1 depleted human cells as model systems.We found that autophagy is impaired in Capns1-deficient cells by immunostaining of the endogenous autophagosome marker LC3 and electron microscopy experiments [4].

References