Open AccessSequestration of Glyceraldehyde‐3‐phosphate Dehydrogenase to Aggregates Formed by Mutant Huntingtin
Author(s) -
WU Junchao,
LIN Fang,
QIN Zhenghong
Publication year - 2007
Publication title -
acta biochimica et biophysica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1111/j.1745-7270.2007.00352.x
Subject(s) - huntingtin , glyceraldehyde 3 phosphate dehydrogenase , mutant , huntingtin protein , chemistry , wild type , microbiology and biotechnology , dehydrogenase , biochemistry , biology , enzyme , gene
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 (htt1‐969‐100Q and httl‐969‐46Q, mutant htt) in human mammary gland carcinoma MCF‐7 cells formed more htt aggregates than that of htt1‐969‐18Q (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.