Alpha 6 integrins promote cytokinesis by regulating the expression of RSK2 and MKLP1
Abstract
ABSTRACT The integrin-mediated interaction of cells with components of the extracellular matrix (ECM) regulates many cellular processes including cell division. Cytokinesis is the last step of cell division and is critical for normal development and tissue homeostasis as it ensures the proper segregation of genetic and cytoplasmic material between daughter cells. Cytokinesis failure leads to defects in development and tissue differentiation, as well as tumorigenesis. Abscission of intercellular bridge that connects presumptive daughter cells is the last step of cell division. The mitotic kinesin-like protein 1 (MKLP1) plays a central role in positioning the abscission machinery. Here, we show that α6 integrins promote successful cytokinesis in salivary gland epithelial cells by regulating the expression of MKLP1. RNAi-mediated depletion of α6 integrins inhibits cytokinesis and the expression of MKLP1 and p90 ribosomal-S6-kinase 2 (RSK2). Depletion of RSK2 results in similar defects in cytokinesis and also inhibits the expression of MKLP1, suggesting that the expression of RSK2 is required downstream of integrins to promote MKLP1 expression and successful cytokinesis. RNAi-mediated depletion of RSK2 in embryonic salivary glands in organ culture also results in the inhibition of cytokinesis and MKLP1 expression, indicating the physiological significance of this pathway.
Related Papers
- → Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis(2014)103 cited
- → Shs1p: A Novel Member of Septin That Interacts with Spa2p, Involved in Polarized Growth inSaccharomyces cerevisiae(1998)101 cited
- → Evidence that a septin diffusion barrier is dispensable for cytokinesis in budding yeast(2011)87 cited
- → Shs1 Plays Separable Roles in Septin Organization and Cytokinesis in Saccharomyces cerevisiae(2007)53 cited
- → Septin Remodeling During Mammalian Cytokinesis(2021)27 cited