The COOH-terminal domain of huntingtin interacts with RhoGEF kalirin and modulates cell survival
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McClory, Hollis
Wang, Xiaolong
Sapp, Ellen
Gatune, Leah W.
Iuliano, Maria
Wu, Chiu-Yi
Nathwani, Gina
Kegel-Gleason, Kimberly B.
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https://doi.org/10.1038/s41598-018-26255-1Metadata
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McClory, Hollis, Xiaolong Wang, Ellen Sapp, Leah W. Gatune, Maria Iuliano, Chiu-Yi Wu, Gina Nathwani, Kimberly B. Kegel-Gleason, Marian DiFiglia, and Xueyi Li. 2018. “The COOH-terminal domain of huntingtin interacts with RhoGEF kalirin and modulates cell survival.” Scientific Reports 8 (1): 8000. doi:10.1038/s41598-018-26255-1. http://dx.doi.org/10.1038/s41598-018-26255-1.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964228/pdf/Terms of Use
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