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OTULIN和SCRIB之间的相互作用揭示了平面细胞极性线性无化在平面细胞极性中的作用

Stephanie M Almeida^1,2, Sofiia Ivantsiv^1,2, Rieko Niibori¹

¹Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Ave, Toronto, ON M5G 1X5, Canada.

Disease models & mechanisms

|August 17, 2023

概括

线性无素链通过影响VANGL2呈现来调节平面细胞极性 (PCP). OTULIN是一种二维基因酶,与SCRIB相互作用并影响PCP,这表明线性泛基因化和发育过程之间存在联系.

科学领域:

细胞生物学细胞生物学
发展生物学发展生物学
分子生物学分子生物学

背景情况:

平面细胞极性 (PCP) 对于发育和恒温至关重要.
PCP依赖于包括VANGL蛋白质在内的复合体的膜呈现,通常由SCRIB指导.
在PCP中线性 (Met1-Ub) 链的功能尚不清楚.

研究的目的:

调查线性无处不在的作用,特别是涉及OTULIN,在PCP信号中.
为了确定OTULIN是否与PCP组件 (如SCRIB) 相互作用.
探索OTULIN和Met1-Ub链对VANGL2贩运和PCP功能的影响.

主要方法:

HEK293基于细胞的相互作用原子分析,以确定OTULIN的相互作用.
对Met1-Ub链与PCP蛋白的关联分析 (VANGL2,PRICKLE1,SCRIB).
在MDCK和MDA-MB-231细胞中缺乏Otulin和功能测试的小鼠胚胎的表型分析.

主要成果:

奥林与SCRIB相互作用;Met1-Ub链与VANGL2和PRICKLE1关联,指导VANGL2的表面呈现.
在小鼠胚胎中失去奥图林会导致神经管形,表明PCP中断.
在激活的PCP复合体中,OTULIN被招募到细胞与细胞的接触中,其损失损害了Wnt5a诱导的filopodia和VANGL2贩运.

结论:

线性 (de) ubiquitination 在PCP信号通路中起着重要的作用.
与PCP组件相关的Met1-Ub链提供了调节PCP的机制.
这项工作将OTULIN依赖的线性无处不在与发育过程联系起来,并为PCP与免疫/炎症通路的整合提供了途径.

关键词:

线性无处不在的存在.线性无处不在的组装复杂.鼠标遗传学鼠标遗传学奥图林 (OTULIN) 是一个古老的城市.平面细胞极性平面细胞极性一个小小的草.

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