Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Curr Opin Cell Biol. 2024 Oct;90:102419. doi: 10.1016/j.ceb.2024.102419. Epub 2024 Aug 22.
The dynamic actin cytoskeleton contributes to many critical biological processes by providing the structural support underlying the morphology of most cells, facilitating intracellular transport, and generating forces required for cell motility and division. To execute many of these functions, actin monomers polymerize into polarized filaments that display different structural and biochemical properties at each end. Filament dynamics are regulated by diverse regulatory proteins which collaborate to dictate rates of elongation and disassembly, particularly at the fast-growing barbed (plus) end. This review highlights the biochemical mechanisms of six barbed end regulatory proteins: formin, profilin, capping protein, IQGAP1, cyclase-associated protein, and twinfilin. We discuss how individual proteins influence actin dynamics and how several intriguing complex assemblies influence the polymerization fate of actin filaments. Understanding these mechanisms offers insights into how actin is regulated in essential cell processes and dysregulated in disease.
动态肌动蛋白细胞骨架通过为大多数细胞的形态提供结构支撑，促进细胞内运输，并产生细胞运动和分裂所需的力，从而为许多关键的生物学过程做出贡献。为了执行许多这些功能，肌动蛋白单体聚合成具有不同结构和生化特性的极化纤维，在每个末端都显示出不同的结构和生化特性。纤维动力学受多种调节蛋白的调节，这些调节蛋白协同作用来决定延伸和组装的速度，特别是在快速生长的刺状（+）末端。这篇综述强调了六种纤维状末端调节蛋白的生化机制：成核蛋白、原肌球蛋白、加帽蛋白、IQGAP1、环化酶相关蛋白和孪生蛋白。我们讨论了单个蛋白如何影响肌动蛋白动力学，以及几种有趣的复杂组装如何影响肌动蛋白纤维的聚合命运。了解这些机制为肌动蛋白在基本细胞过程中的调节以及在疾病中的失调提供了深入的认识。
