Nakamura Mitsutoshi, Verboon Jeffrey M, Parkhurst Susan M
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
J Cell Biol. 2017 Dec 4;216(12):3959-3969. doi: 10.1083/jcb.201704145. Epub 2017 Sep 18.
Like tissues, single cells are subjected to continual stresses and damage. As such, cells have a robust wound repair mechanism comprised of dynamic membrane resealing and cortical cytoskeletal remodeling. One group of proteins, the Rho family of small guanosine triphosphatases (GTPases), is critical for this actin and myosin cytoskeletal response in which they form distinct dynamic spatial and temporal patterns/arrays surrounding the wound. A key mechanistic question, then, is how these GTPase arrays are formed. Here, we show that in the cell wound repair model Rho GTPase arrays form in response to prepatterning by Rho guanine nucleotide exchange factors (RhoGEFs), a family of proteins involved in the activation of small GTPases. Furthermore, we show that Annexin B9, a member of a class of proteins associated with the membrane resealing, is involved in an early, Rho family-independent, actin stabilization that is integral to the formation of one RhoGEF array. Thus, Annexin proteins may link membrane resealing to cytoskeletal remodeling processes in single cell wound repair.
与组织一样，单个细胞也会不断受到压力和损伤。因此，细胞拥有一种强大的伤口修复机制，该机制由动态膜重封和皮质细胞骨架重塑组成。一类蛋白质，即小GTP酶（GTPases）的Rho家族，对于这种肌动蛋白和肌球蛋白细胞骨架反应至关重要，在该反应中，它们围绕伤口形成独特的动态空间和时间模式/阵列。那么，一个关键的机制问题是这些GTP酶阵列是如何形成的。在这里，我们表明，在细胞伤口修复模型中，Rho GTP酶阵列是响应Rho鸟嘌呤核苷酸交换因子（RhoGEFs）的预模式而形成的，RhoGEFs是一类参与小GTP酶激活的蛋白质家族。此外，我们表明膜联蛋白B9，一类与膜重封相关的蛋白质成员，参与了早期的、不依赖Rho家族的肌动蛋白稳定过程，这是一个RhoGEF阵列形成所必需的过程。因此，膜联蛋白可能在单细胞伤口修复中将膜重封与细胞骨架重塑过程联系起来。
