Ric-8 proteins are molecular chaperones that direct nascent G protein α subunit membrane association.
Ric-8 proteins are molecular chaperones that direct nascent G protein α subunit membrane association.
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RIC-8蛋白是直接新生G蛋白α亚基膜关联的分子伴侣。
DOI：
10.1126/scisignal.2002223
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发表时间：
2011-11-22
影响因子：
7.3
通讯作者：
Tall GG
中科院分区：
文献类型：
--
作者：
Gabay M;Pinter ME;Wright FA;Chan P;Murphy AJ;Valenzuela DM;Yancopoulos GD;Tall GG
Ric-8A（对胆碱酯酶8A抑制剂的抗性）和Ric-8B是鸟嘌呤核苷酸交换因子，其通过未知机制增强不同的异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）信号传导途径。由于小鼠中Ric-8A或Ric-8B的转基因破坏导致早期胚胎致死，我们从这些小鼠的囊胚中获得了可存活的Ric-8A或Ric-8B缺失的胚胎干（ES）细胞系。我们在Ric-8A−/− ES细胞中观察到多效性G蛋白信号传导缺陷，这是由于Gαi，Gαq和Gα13蛋白的稳态量减少到野生型细胞的5%以下。与野生型细胞相比，Ric-8A−/−细胞中Gαs和总Gβ蛋白的量部分减少，Ric-8B−/−细胞中仅Gαs的量大幅减少。编码G蛋白α亚基的mRNA丰度在Ric-8A或Ric-8B缺失的情况下基本不变。G蛋白的质膜驻留持续在Ric-8的情况下，但显着减少相比，在野生型细胞。内源性Gαi和Gαq在Ric-8A−/−细胞中被有效翻译，但整合到内膜中的能力很差;然而，到达膜的G蛋白α亚基的数量减少，仍然与新生的Gβγ结合。最后，与野生型细胞相比，Gαi、Gαq和Gβ1蛋白在Ric-8A−/−细胞中的降解速率加快。总之，这些数据表明Ric-8蛋白是新生Gα亚基与细胞膜初始结合所需的分子伴侣。
Ric-8A (resistance to inhibitors of cholinesterase 8A) and Ric-8B are guanine nucleotide exchange factors that enhance different heterotrimeric guanine nucleotide–binding protein (G protein) signaling pathways by unknown mechanisms. Because transgenic disruption of Ric-8A or Ric-8B in mice caused early embryonic lethality, we derived viable Ric-8A– or Ric-8B–deleted embryonic stem (ES) cell lines from blastocysts of these mice. We observed pleiotropic G protein signaling defects in Ric-8A−/− ES cells, which resulted from reduced steady-state amounts of Gαi, Gαq, and Gα13 proteins to <5% of those of wild-type cells. The amounts of Gαs and total Gβ protein were partially reduced in Ric-8A−/− cells compared to those in wild-type cells, and only the amount of Gαs was reduced substantially in Ric-8B−/− cells. The abundances of mRNAs encoding the G protein α subunits were largely unchanged by loss of Ric-8A or Ric-8B. The plasma membrane residence of G proteins persisted in the absence of Ric-8 but was markedly reduced compared to that in wild-type cells. Endogenous Gαi and Gαq were efficiently translated in Ric-8A−/− cells but integrated into endomembranes poorly; however, the reduced amounts of G protein α subunits that reached the membrane still bound to nascent Gβγ. Finally, Gαi, Gαq, and Gβ1 proteins exhibited accelerated rates of degradation in Ric-8A−/− cells compared to those in wild-type cells. Together, these data suggest that Ric-8 proteins are molecular chaperones required for the initial association of nascent Gα subunits with cellular membranes.
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DOI：
10.1073/pnas.87.2.568
发表时间：
1990-01-01
影响因子：
11.1
作者：
JONES, TLZ;SIMONDS, WF;SPIEGEL, AM
通讯作者：
SPIEGEL, AM
影响因子：
4.6
作者：
Afshar, K;Willard, FS;Gönczy, P
通讯作者：
Gönczy, P
影响因子：
5.6
作者：
Klattenhoff, C;Montecino, M;Olate, J
通讯作者：
Olate, J
影响因子：
9.2
作者：
Liu, QH;Li, MZ;Elledge, SJ
通讯作者：
Elledge, SJ
影响因子：
4.8
作者：
Krumins, AM;Gilman, AG
通讯作者：
Gilman, AG