Sequestration of Glyceraldehyde-3-phosphate Dehydrogenase to Aggregates Formed by Mutant Huntingtin  

作　　者：Junchao WU Fang LIN Zhenghong QIN 

机构地区：[1]Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, China

出　　处：《Acta Biochimica et Biophysica Sinica》2007年第11期885-890,共6页生物化学与生物物理学报（英文版）

基　　金：This work was partially supported by the grants from the National Natural Science Foundation of China （No. 30370506） and the Specialized Research Fund for the Doctoral Program of Higher Education, China （No. 20050285017）

摘　　要：Glyceraldehyde-3-phosphate dehydrogenase （GAPDH） has been reported to interact with proteins containing the polyglutamine （polyQ） domain. The present study was undertaken to evaluate the potential contributions of the polyQ and polyproline （polyP） domains to the co-localization of mutant huntingtin （htt） and GAPDH. Overexpression of N-terminal htt （1-969 amino acids） with 100Q and 46Q （httl-969- 100Q and httl-969-46Q, mutant htt） in human mammary gland carcinoma MCF-7 cells formed more htt aggregates than that of httl-969-18Q （wild-type htt）. The co-localization of GAPDH with htt aggregates was found in the cells expressing mutant but not wild-type htt. Deletion of the polyP region in the N-terminal htt had no effect on the co-localization of GAPDH and mutant htt aggregates. These results suggest that the polyQ domain, but not the polyP domain, plays a role in the sequestration of GAPDH to aggregates by mutant htt. This effect might contribute to the dysfunction of neurons caused by mutant htt in Huntington＇s disease.Glyceraldehyde-3-phosphate dehydrogenase （GAPDH） has been reported to interact with proteins containing the polyglutamine （polyQ） domain. The present study was undertaken to evaluate the potential contributions of the polyQ and polyproline （polyP） domains to the co-localization of mutant huntingtin （htt） and GAPDH. Overexpression of N-terminal htt （1-969 amino acids） with 100Q and 46Q （httl-969- 100Q and httl-969-46Q, mutant htt） in human mammary gland carcinoma MCF-7 cells formed more htt aggregates than that of httl-969-18Q （wild-type htt）. The co-localization of GAPDH with htt aggregates was found in the cells expressing mutant but not wild-type htt. Deletion of the polyP region in the N-terminal htt had no effect on the co-localization of GAPDH and mutant htt aggregates. These results suggest that the polyQ domain, but not the polyP domain, plays a role in the sequestration of GAPDH to aggregates by mutant htt. This effect might contribute to the dysfunction of neurons caused by mutant htt in Huntington＇s disease.

关 键 词：HUNTINGTIN GAPDH POLYGLUTAMINE POLYPROLINE 

分 类 号：Q55[生物学—生物化学]