磷脂酰肌醇 4-磷酸控制 Rab GEF Sec2p 的膜募集和调节开关。
Phosphatidylinositol 4-phosphate controls both membrane recruitment and a regulatory switch of the Rab GEF Sec2p.
机构信息
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
出版信息
Dev Cell. 2010 May 18;18(5):828-40. doi: 10.1016/j.devcel.2010.03.016.
Sec2p is the guanine nucleotide exchange factor (GEF) that activates the Rab GTPase Sec4p on secretory vesicles. Sec2p also binds a Rab acting earlier in the secretory pathway, Ypt32-GTP, forming a Rab GEF cascade. Ypt32p and the Sec4p effector Sec15p (a component of the exocyst complex) compete for binding to Sec2p. Indeed Ypt32p initially recruits Sec2p, but subsequently allows a handoff of active Sec2p/Sec4p to Sec15p. Intriguingly, Golgi-associated phosphatidylinositol 4-phosphate (PI4P) works together with Ypt32-GTP in this context. PI4P inhibits Sec2p-Sec15p interactions, promoting recruitment of Sec2p by Ypt32p as secretory vesicles form. However, PI4P levels appear to decline as vesicles reach secretory sites, allowing Sec15p to replace Ypt32p as vesicles mature. In this way, the regulation of PI4P levels may switch Sec2p/Sec4p function during vesicle maturation, from a Rab GEF recruitment cascade involving Ypt32p to an effector positive feedback loop involving Sec15p.
Sec2p 是一种鸟嘌呤核苷酸交换因子（GEF），可激活分泌小泡上的 Rab GTPase Sec4p。Sec2p 还与 Rab 结合，Rab 在分泌途径中更早起作用，Ypt32-GTP，形成 Rab GEF 级联。Ypt32p 和 Sec4p 效应物 Sec15p（外泌体复合物的一个组成部分）竞争与 Sec2p 的结合。事实上，Ypt32p 最初招募 Sec2p，但随后允许将活性 Sec2p/Sec4p 递交给 Sec15p。有趣的是，高尔基体相关的磷脂酰肌醇 4-磷酸（PI4P）在这种情况下与 Ypt32-GTP 一起发挥作用。PI4P 抑制 Sec2p-Sec15p 相互作用，促进 Ypt32p 募集 Sec2p 形成分泌小泡。然而，随着小泡到达分泌部位，PI4P 水平似乎下降，允许 Sec15p 取代 Ypt32p 作为小泡成熟。通过这种方式，PI4P 水平的调节可能会在小泡成熟过程中切换 Sec2p/Sec4p 的功能，从涉及 Ypt32p 的 Rab GEF 募集级联到涉及 Sec15p 的效应物正反馈回路。
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