Septins are a unique family of GTPases, which were discovered 50 years ago as essential genes for the asymmetric cell shape and division of budding yeast. Septins assemble into filamentous nonpolar polymers, which associate with distinct membrane macrodomains and subpopulations of actin filaments and microtubules. While structurally a cytoskeleton-like element, septins function predominantly as spatial regulators of protein localization and interactions. Septin scaffolds and barriers have provided a long-standing paradigm for the generation and maintenance of asymmetry in cell membranes. Septins also promote asymmetry by regulating the spatial organization of the actin and microtubule cytoskeleton, and biasing the directionality of membrane traffic. In this 50th anniversary perspective, we highlight how septins have conserved and adapted their roles as effectors of membrane and cytoplasmic asymmetry across fungi and animals. We conclude by outlining principles of septin function as a module of symmetry breaking, which alongside the monomeric small GTPases provides a core mechanism for the biogenesis of molecular asymmetry and cell polarity.

Septins是GTPases的独特家族，其在50年前被发现为不对称细胞形状和发芽酵母分裂的必需基因。Septins组装成丝状非极性聚合物，其与不同的膜宏结构域和肌动蛋白丝和微管的亚群相关。虽然在结构上是细胞骨架样的元件，但septins主要充当蛋白质定位和相互作用的空间调节剂。Septin支架和屏障为细胞膜的不对称性产生和维持提供了长期的范例。隔蛋白还通过调节肌动蛋白和微管细胞骨架的空间组织并偏向膜运输的方向性来促进不对称性。从这个50周年的角度来看，我们着重介绍了Septin如何在真菌和动物中保守和适应其作为膜和细胞质不对称效应子的作用。我们通过概述Septin作为对称性破坏模块的原理进行总结，它与单体小GTPase一起为分子非对称性和细胞极性的生物发生提供了核心机制。