The Actin Cytoskeleton and Cell Survival

摘要

The actin cytoskeleton supports the structural integrity of the cell, drives motility and facilitates signaling from growth factors to their effector pathways. Over the last decade the actin cytoskeleton has also been shown to communicate directly to the cell survival machinery. Actin communication predates the well documented Bcl-2 pro-survival pathway since it is the major pathway in yeast. Three examples are discussed in this review. First, a cytoskeletal signaling kinase, Pak, regulates Raf-1 which translocates and phosphorylates Bad, a Bcl-2 binding protein to prevent cell death. In the second example actin is cleaved and transported to mitochondria to promote cell death, while in the third example actin binding proteins including cofilin and CAP1 translocate to mitochondria, again to promote cell death. This pathway shows some similarities to the pathway in yeast. Although there are many gaps in our understanding of cytoskeletal regulation of apoptosis, two properties characterize each of these examples. First, all known cases involve direct communication between the cytoskeleton and the mitochondria and second, the cytoskeleton directs the translocation of proteins, often actin itself, to mitochondria.