Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA activation induced by collagen III stimulation.
Mechanism for adhesion G protein-coupled receptor GPR56-mediated RhoA activation induced by collagen III stimulation.
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DOI：
10.1371/journal.pone.0100043
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Piao X
中科院分区：
文献类型：
--
作者：
Luo R;Jeong SJ;Yang A;Wen M;Saslowsky DE;Lencer WI;Araç D;Piao X
GPR 56是粘附G蛋白偶联受体（GPCR）家族的成员。尽管GPR 56在大脑发育中的重要性，其中突变导致称为双侧额顶叶多微回症（BFPP）的破坏性人脑畸形，但信号传导机制在很大程度上仍然未知。与许多其他粘附GPCR一样，GPR 56通过GPCR自蛋白水解诱导（GAIN）结构域切割成N-和C-末端片段（GPR 56 N和GPR 56 C）;然而，这种切割的生物学意义是难以捉摸的。利用最近发现的GPR 56配体和BFPP相关突变的存在，我们研究了GPR 56信号传导的分子机制。我们证明，配体结合释放GPR 56 N从膜结合GPR 56 C和触发协会的GPR 56 C与脂筏和RhoA激活。此外，BFPP相关突变之一L 640 R不影响III型胶原诱导的GPR 56脂筏结合。相反，它特异性地消除胶原III介导的RhoA激活。总之，这些发现揭示了一种新的信号传导机制，可能适用于粘附GPCR家族的其他成员。
GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Despite the importance of GPR56 in brain development, where mutations cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP), the signaling mechanism(s) remain largely unknown. Like many other adhesion GPCRs, GPR56 is cleaved via a GPCR autoproteolysis-inducing (GAIN) domain into N- and C-terminal fragments (GPR56N and GPR56C); however, the biological significance of this cleavage is elusive. Taking advantage of the recent identification of a GPR56 ligand and the presence of BFPP-associated mutations, we investigated the molecular mechanism of GPR56 signaling. We demonstrate that ligand binding releases GPR56N from the membrane-bound GPR56C and triggers the association of GPR56C with lipid rafts and RhoA activation. Furthermore, one of the BFPP-associated mutations, L640R, does not affect collagen III-induced lipid raft association of GPR56. Instead, it specifically abolishes collagen III-mediated RhoA activation. Together, these findings reveal a novel signaling mechanism that may apply to other members of the adhesion GPCR family.
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影响因子：
64.8
作者：
Hollenstein, Kaspar;Kean, James;Marshall, Fiona H.
通讯作者：
Marshall, Fiona H.
DOI：
10.1073/pnas.92.22.10094
发表时间：
1995-10-24
影响因子：
11.1
作者：
LENCER, WI;MOE, S;MADARA, JL
通讯作者：
MADARA, JL
影响因子：
3.7
作者：
Luo R;Jin Z;Deng Y;Strokes N;Piao X
通讯作者：
Piao X
影响因子：
3.5
作者：
Jin, Zhaohui;Tietjen, Ian;Piao, Xianhua
通讯作者：
Piao, Xianhua
影响因子：
11.4
作者：
Arac, Demet;Boucard, Antony A.;Bolliger, Marc F.;Nguyen, Jenna;Soltis, S. Michael;Suedhof, Thomas C.;Brunger, Axel T.
通讯作者：
Brunger, Axel T.