Disruption of the murine calpain small subunit gene, Capn4:: Calpain is essential for embryonic development but not for cell growth and division
Disruption of the murine calpain small subunit gene, Capn4:: Calpain is essential for embryonic development but not for cell growth and division
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DOI：
10.1128/mcb.20.12.4474-4481.2000
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发表时间：
2000-06-01
影响因子：
5.3
通讯作者：
Greer, PA
中科院分区：
文献类型：
--
作者：
Arthur, JSC;Elce, JS;Greer, PA
钙蛋白酶是一类钙离子依赖的细胞内半胱氨酸蛋白酶家族，包括广泛表达的m-和m-钙蛋白酶。两种钙蛋白酶都是异源二聚体，由编码基因Capn1和Capn2编码的80 kDa大催化亚基和共同的28 kDa小调控亚基(Capn4)组成。目前尚不清楚u-和m-calain的生理作用和可能的功能差异，但推测的功能包括参与细胞分裂和迁移，整合素介导的信号转导，细胞凋亡，以及对细胞控制蛋白如细胞周期蛋白D1和p53的调控。纯合子破坏小鼠的Capn4基因消除了u-和m-calain的活性，但这不影响培养的胚胎干细胞或胚胎成纤维细胞的存活和增殖，也不影响器官发生的早期阶段。然而，突变胚胎在妊娠中期死亡，表现为心血管系统缺陷、出血和红系祖细胞聚集。
Calpains are a family of Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed mu- and m-calpains. 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). The physiological roles and possible functional distinctions of mu- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53. 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. However, mutant embryos died at midgestation and displayed defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors.