Fam49/CYRI interacts with Rac1 and locally suppresses protrusions.
Fam49/CYRI interacts with Rac1 and locally suppresses protrusions.
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DOI：
10.1038/s41556-018-0198-9
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发表时间：
2018-10
影响因子：
21.3
通讯作者：
Machesky LM
中科院分区：
文献类型：
--
作者：
Fort L;Batista JM;Thomason PA;Spence HJ;Whitelaw JA;Tweedy L;Greaves J;Martin KJ;Anderson KI;Brown P;Lilla S;Neilson MP;Tafelmeyer P;Zanivan S;Ismail S;Bryant DM;Tomkinson NCO;Chamberlain LH;Mastick GS;Insall RH;Machesky LM
驱动细胞迁移的基于肌动蛋白的突起通过正反馈得到加强，但目前尚不清楚细胞如何限制突起的最终大小或限制正信号以允许它们分裂或缩回。我们已经确定了一个进化上保守的调节器的突起机制，我们命名为CYRI（CYFIP相关的Rac相互作用）。CYRI通过一个共同的基序，也发现在CYFIP，未知功能DUF 1394的结构域，我们证明DUF 1394是一个新的类的Rac 1结合模块的激活Rac 1特异性结合。CYRI耗竭的细胞具有富含Scar/WAVE的宽板状伪足，但表现出降低的扩张-收缩动力学。光遗传学Rac 1激活诱导的伪足在CYRI不存在的情况下更大，寿命更长。相反，CYRI过表达抑制了活性Scar/WAVE复合物向细胞边缘的募集，导致短暂的非生产性突起。因此，CYRI在细胞行为中的作用是通过抑制Scar/WAVE诱导的肌动蛋白来聚焦正突起信号并调节伪足复杂性和动力学。因此，它的行为就像一个“局部抑制剂”预测和广泛接受的数学模型描述，但以前没有在活细胞中确定。CYRI对于需要突起的极性和可塑性的生物过程是重要的，包括上皮囊肿的定向迁移和极化。
Actin-based protrusions driving cell migration are reinforced through positive feedback, but it is unclear how the cell restricts the eventual size of protrusions or limits positive signals to allow them to split or retract. We have identified an evolutionarily conserved regulator of the protrusion machinery, which we name CYRI (CYFIP-related Rac interactor). CYRI binds specifically to activated Rac1 via a common motif that is also found in CYFIP, the Domain of Unknown Function DUF1394; we demonstrate that DUF1394 is a new class of Rac1 binding module. CYRI-depleted cells have broad lamellipodia enriched in Scar/WAVE, but exhibit reduced protrusion-retraction dynamics. Pseudopods induced by optogenetic Rac1 activation are larger and longer-lived in the absence of CYRI. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE complex to the cell edge, resulting in short-lived, unproductive protrusions. CYRI’s role in cell behaviour is therefore to focus positive protrusion signals and regulate pseudopod complexity and dynamics by inhibiting Scar/WAVE induced actin. As such it behaves like a “local inhibitor” predicted and described in widely accepted mathematical models, but not previously identified in living cells. CYRI is important for biological processes requiring polarity and plasticity of protrusions, including directional migration and polarization of epithelial cysts.
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肌动蛋白调节波复合物的结构和控制。
影响因子：
64.8
作者：
Chen, Zhucheng;Borek, Dominika;Padrick, Shae B.;Gomez, Timothy S.;Metlagel, Zoltan;Ismail, Ayman M.;Umetani, Junko;Billadeau, Daniel D.;Otwinowski, Zbyszek;Rosen, Michael K.
通讯作者：
Rosen, Michael K.
影响因子：
21.3
作者：
Andrew, Natalie;Insall, Robert H.
通讯作者：
Insall, Robert H.
影响因子：
64.8
作者：
Dang, Irene;Gorelik, Roman;Gautreau, Alexis
通讯作者：
Gautreau, Alexis
影响因子：
1.8
作者：
Kollmar M;Lbik D;Enge S
通讯作者：
Enge S
DOI：
10.1146/annurev-cellbio-100616-060739
发表时间：
2017-10-06
影响因子：
11.3
作者：
Devreotes PN;Bhattacharya S;Edwards M;Iglesias PA;Lampert T;Miao Y
通讯作者：
Miao Y