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First published online May 8, 2008

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An autophagic role for Rab5

In macroautophagy, proteins are cleared from the cytoplasm by engulfment in a double-membraned structure (the autophagosome). In Huntington disease, for example, macroautophagy mediates the clearance of the aggregation-prone mutant of the protein huntingtin, which contains an abnormally long polyglutamine tract. David Rubinsztein and colleagues (p. 1649) now describe a new modulator of the degradation of huntingtin by macroautophagy – the small GTPase Rab5, previously better known as a regulator of early endocytosis. The authors show that, in mammalian cells that express a mutant huntingtin exon 1 fragment, Rab5 activity significantly decreases toxicity. Moreover, Rab5 overexpression decreases the characteristic photoreceptor degeneration that is seen in flies that express mutant huntingtin. The authors show that Rab5 is a member of a complex that also contains the proteins beclin 1 and Vps34, and that associates with autophagosomal precursors. When Rab5 is inhibited, autophagosomal precursors accumulate in cells, whereas the number of autophagic vacuoles decreases. By contrast, autophagic vacuoles accumulate when endocytosis is inhibited. The authors conclude that Rab5 is important in the early stages of macroautophagy, and that this role is distinct from its endocytic function.

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Related articles in JCS:

Rab5 modulates aggregation and toxicity of mutant huntingtin through macroautophagy in cell and fly models of Huntington disease

Brinda Ravikumar, Sara Imarisio, Sovan Sarkar, Cahir J. O'Kane, and David C. Rubinsztein
JCS 2008 121: 1649-1660. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?