Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dev Cell. 2013 Jul 29;26(2):148-61. doi: 10.1016/j.devcel.2013.06.015.
Asymmetric cell division plays a crucial role in cell differentiation, unequal replicative senescence, and stem cell maintenance. In budding yeast, the identities of mother and daughter cells begin to diverge at bud emergence when distinct plasma-membrane domains are formed and separated by a septin ring. However, the mechanisms underlying this transformation remain unknown. Here, we show that septins recruited to the site of polarization by Cdc42-GTP inhibit Cdc42 activity in a negative feedback loop, and this inhibition depends on Cdc42 GTPase-activating proteins. Combining live-cell imaging and computational modeling, we demonstrate that the septin ring is sculpted by polarized exocytosis, which creates a hole in the accumulating septin density and relieves the inhibition of Cdc42. The nascent ring generates a sharp boundary that confines the Cdc42 activity and exocytosis strictly to its enclosure and thus clearly delineates the daughter cell identity. Our findings define a fundamental mechanism underlying eukaryotic cell fate differentiation.
不对称细胞分裂在细胞分化、不等复制性衰老和干细胞维持中起着关键作用。在出芽酵母中，当形成不同的质膜区域并被隔膜环隔开时，母细胞和子细胞的身份在芽出现时开始分化。然而，这种转变的机制尚不清楚。在这里，我们表明，由 Cdc42-GTP 募集到极化位点的隔膜抑制了负反馈环中的 Cdc42 活性，而这种抑制依赖于 Cdc42 GTP 酶激活蛋白。通过活细胞成像和计算建模，我们证明了由极化胞吐作用塑造的隔膜环在积累的隔膜密度中产生一个孔，从而解除了对 Cdc42 的抑制。新生的环产生一个锐利的边界，将 Cdc42 活性和胞吐作用严格限制在其范围内，从而明确划定了子细胞的身份。我们的发现定义了真核细胞命运分化的基本机制。
