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uCalpain and friends in Cell spread

2019.8.04
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zhaochenxu

致力于为分析测试行业奉献终身

m_uCalpainPathway.gif

The mammalian calpain gene family curently contains 13 distinct large subunit products most of which complex with one of two smaller 30kDa subunits. ( An excellent introduction to the Calpain family can be found on a web site created by Valery Thompson http://ag.arizona.edu/calpains/index.html ) Spreading cells display newly transiently formed integrin adhesion clusters containing Calpain1 (mu-Calpain), cleaved Talin, B3-Integrin and SPTAN1(Spectrin). Recruitment of Rac to these clusters leads to the activation of Rac and the formation of Rac-induced Focal clusters. The Calpain1 in the integrin clusters initially inactivates RhoA allowing for the formation of lamellipodia. The subsequent activation of newly synthesized RhoA transforms these clusters into Focal Adhesion Complexes and the formation of contractile actin-myosin stress fibers. These mature adhesions do not contain calpain.

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REFERENCES: Bialkowska K, Kulkarni S, Du X, Goll DE, Saido TC, Fox JE. Evidence that beta3 integrin-induced Rac activation involves the calpain-dependent formation of integrin clusters that are distinct from the focal complexes and focal adhesions that form as Rac and RhoA become active. J Cell Biol. 2000 Oct 30;151(3):685-96. Glading A, Lauffenburger DA, Wells A. Cutting to the chase: calpain proteases in cell motility. Trends Cell Biol. 2002 Jan;12(1):46-54. Review. Klemke RL, Cai S, Giannini AL, Gallagher PJ, de Lanerolle P, Cheresh DA. Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol. 1997 Apr 21;137(2):481-92. Kulkarni S, Goll DE, Fox JE. Calpain cleaves RhoA generating a dominant-negative form that inhibits integrin-induced actin filament assembly and cell spreading. J Biol Chem. 2002 Jul 5;277(27):24435-41. Kulkarni S, Saido TC, Suzuki K, Fox JE. Calpain mediates integrin-induced signaling at a point upstream of Rho family members. J Biol Chem. 1999 Jul 23;274(30):21265-75.


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