Cdc42, a conserved regulator of cell polarity, is activated by two GEFs, Gef1 and Scd1, in fission yeast. Why the cell needs two GEFs is unclear, given that they are partially redundant and activate the same GTPase. Using the GEF localization pattern during cytokinesis as a paradigm, we report a novel interplay between Gef1 and Scd1 that spatially modulates Cdc42. We find that Gef1 promotes Scd1 localization to the division site during cytokinesis through recruitment of the scaffold protein Scd2, via a Cdc42 feedforward pathway. Similarly, during interphase Gef1 promotes Scd1 recruitment at the new end to enable the transition from monopolar to bipolar growth. Reciprocally, Scd1 restricts Gef1 localization to prevent ectopic Cdc42 activation during cytokinesis to promote cell separation, and to maintain cell shape during interphase. Our findings reveal an elegant regulatory pattern in which Gef1 primes Cdc42 activation at new sites to initiate Scd1-dependent polarized growth, while Scd1 restricts Gef1 to sites of polarization. We propose that crosstalk between GEFs is a conserved mechanism that orchestrates Cdc42 activation during complex cellular processes.This article has an associated First Person interview with the first author of the paper.

中文翻译：

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GEF之间的新型相互作用在裂变酵母的细胞极性和胞质分裂过程中协调了Cdc42的活性。

Cdc42是一种保守的细胞极性调节剂，在裂殖酵母中被两个GEF（Gef1和Scd1）激活。该单元为何需要两个GEF尚不清楚，因为它们是部分冗余并激活相同的GTPase。使用胞质分裂过程中的GE​​F本地化模式作为范例，我们报告Gef1和Scd1之间的新型相互作用，在空间上调节Cdc42。我们发现Gef1通过Cdc42前馈途径募集支架蛋白Scd2，从而在胞质分裂过程中促进Scd1定位到分裂位点。同样，在相间期，Gef1在新的末端促进Scd1募集，以实现从单极生长向双极生长的过渡。相反，Scd1限制Gef1定位，以防止胞质分裂过程中异位Cdc42活化，从而促进细胞分离，并在相间期维持细胞形状。我们的发现揭示了一种优雅的调节模式，其中Gef1在新位点引发Cdc42激活以启动Scd1依赖性极化生长，而Scd1将Gef1限制在极化位点。我们认为，GEF之间的串扰是一种在复杂细胞过程中协调Cdc42激活的保守机制。