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Calretinin interacts with huntingtin and reduces mutant huntingtin‐caused cytotoxicity
Author(s) -
Dong Gaofeng,
Gross Kylie,
Qiao Fangfang,
Ferguson Justine,
Callegari Eduardo A.,
Rezvani Khosrow,
Zhang Dong,
Gloeckner Christian J.,
Ueffing Marius,
Wang Hongmin
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07919.x
Subject(s) - huntingtin , huntingtin protein , gene knockdown , microbiology and biotechnology , biology , trinucleotide repeat expansion , colocalization , immunoprecipitation , mutant , neurodegeneration , chemistry , cell culture , biochemistry , gene , genetics , allele , medicine , disease , pathology
Huntington's disease ( HD ) is a devastating neurodegenerative disorder caused by an expansion of CAG trinucleotide repeats encoding for polyglutamine (polyQ) in the huntingtin ( Htt ) gene. Despite considerable effort, the mechanisms underlying the toxicity of the mutated Htt protein remains largely uncertain. To identify novel therapeutic targets, we recently employed the approach of tandem affinity purification and discovered that calretinin (Cr), a member of the EF ‐hand family of calcium‐binding proteins, is preferentially associated with mHtt, although it also interacts with wild‐type Htt. These observations were supported by coimmunoprecipitation and by colocalization of Cr with mHtt in neuronal cultures. Over‐ expression of Cr reduced mHtt‐caused cytotoxicity in both non‐neuronal and neuronal cell models of HD , whereas knockdown of Cr expression in the cells enhanced mHtt‐caused neuronal cell death. In addition, over‐expression of Cr was also associated with reduction of intracellular free calcium and activation of Akt. These results suggest that Cr may be a potential therapeutic target for treatment of HD .