Whitelaw Jamie A, Lilla Sergio, Paul Nikki R, Fort Loic, Zanivan Sara, Machesky Laura M
CRUK Beatson Institute, University of Glasgow, Glasgow, UK.
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Commun Integr Biol. 2019 Jul 23;12(1):112-118. doi: 10.1080/19420889.2019.1643665. eCollection 2019.
Fam49 proteins, now referred to as CYRI (CYFIP-related Rac Interactor), are evolutionarily conserved across many phyla. Their closest relative by amino acid sequence is CYFIP, as both proteins contain a domain of unknown function DUF1394. We recently showed that CYRI and the DUF1394 can mediate binding to Rac1 and evidence is building to suggest that CYRI plays important roles in cell migration, chemotaxis and pathogen entry into cells. Here we discuss how CYRI proteins fit into the current framework of the control of actin dynamics by positive and negative feedback loops containing Rac1, the Scar/WAVE Complex, the Arp2/3 Complex and branched actin. We also provide data regarding the interaction between Rac1 and CYRI in an unbiassed mass spectrometry screen for interactors of an active mutant of Rac1.
Fam49蛋白，现称为CYRI（CYFIP相关的Rac相互作用蛋白），在许多门中都具有进化保守性。按氨基酸序列，它们与CYFIP关系最为密切，因为这两种蛋白都含有一个功能未知的结构域DUF1394。我们最近发现CYRI和DUF1394可以介导与Rac1的结合，并且越来越多的证据表明CYRI在细胞迁移、趋化作用以及病原体进入细胞过程中发挥重要作用。在此我们讨论CYRI蛋白如何融入当前由包含Rac1、Scar/WAVE复合体、Arp2/3复合体和分支肌动蛋白的正负反馈环控制肌动蛋白动力学的框架中。我们还提供了在针对Rac1活性突变体相互作用蛋白的无偏差质谱筛选中关于Rac1与CYRI相互作用的数据。
