The COOH-terminal domain of huntingtin interacts with RhoGEF kalirin and modulates cell survival.
The COOH-terminal domain of huntingtin interacts with RhoGEF kalirin and modulates cell survival.
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DOI：
10.1038/s41598-018-26255-1
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发表时间：
2018-05-22
影响因子：
4.6
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
McClory H;Wang X;Sapp E;Gatune LW;Iuliano M;Wu CY;Nathwani G;Kegel-Gleason KB;DiFiglia M;Li X
Human huntingtin (Htt) contains 3144 amino acids and has an expanded polyglutamine region near the NH2-terminus in patients with Huntington’s disease. While numerous binding partners have been identified to NH2-terminal Htt, fewer proteins are known to interact with C-terminal domains of Htt. Here we report that kalirin, a Rac1 activator, is a binding partner to C-terminal Htt. Kalirin and Htt co-precipitated from mouse brain endosomes and co-localized at puncta in NRK and immortalized striatal cells and primary cortical neurons. We mapped the interaction domains to kalirin674-1272 and Htt2568-3144 and determined that the interaction between kalirin and Htt was independent of HAP1, a known interactor for Htt and kalirin. Kalirin precipitated with mutant Htt was more abundant than with wild-type Htt and had a reduced capacity to activate Rac1 when mutant Htt was present. Expression of Htt2568-3144 caused cytotoxicity, partially rescued by co-expressing kalirin674-1272 but not other regions of kalirin. Our study suggests that the interaction of kalirin with the C-terminal region of Htt influences the function of kalirin and modulates the cytotoxicity induced by C-terminal Htt.
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影响因子：
7.1
作者：
McClory H;Williams D;Sapp E;Gatune LW;Wang P;DiFiglia M;Li X
通讯作者：
Li X
影响因子：
5.3
作者：
Li, Xueyi;Standley, Clive;DiFiglia, Marian
通讯作者：
DiFiglia, Marian
影响因子：
64.8
作者：
LI, XJ;LI, SH;ROSS, CA
通讯作者：
ROSS, CA
影响因子：
11.4
作者：
El-Daher, Marie-Therese;Hangen, Emilie;Saudou, Frederic
通讯作者：
Saudou, Frederic
影响因子：
5.3
作者：
Lynch, Gary;Kramar, Eniko A.;Simmons, Danielle A.
通讯作者：
Simmons, Danielle A.