14-3-3 and aggresome formation: Implications in neurodegenerative diseases |
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Authors: | Baohui Jia Yuying Wu Yi Zhou |
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Institution: | 1Department of Biomedical Sciences; Florida State University College of Medicine; Tallahassee, FL USA;2Guanganmen Hospital; China Academy of Chinese Medical Sciences; Beijing, China |
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Abstract: | Protein misfolding and aggregation underlie the pathogenesis of many neurodegenerative diseases. In addition to chaperone-mediated refolding and proteasomal degradation, the aggresome-macroautophagy pathway has emerged as another defense mechanism for sequestration and clearance of toxic protein aggregates in cells. Previously, the 14-3-3 proteins were shown to be indispensable for the formation of aggresomes induced by mutant huntingtin proteins. In a recent study, we have determined that 14-3-3 functions as a molecular adaptor to recruit chaperone-associated misfolded proteins to dynein motors for transport to aggresomes. This molecular complex involves a dimeric binding of 14-3-3 to both the dynein-intermediate chain (DIC) and an Hsp70 co-chaperone Bcl-2-associated athanogene 3 (BAG3). As 14-3-3 has been implicated in various neurodegenerative diseases, our findings may provide mechanistic insights into its role in managing misfolded protein stress during the process of neurodegeneration. |
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Keywords: | 14-3-3 aggresomes protein misfolding protein aggregation chaperones inclusion bodies neurodegeneration |
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