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Comment
. 2017 Apr 28;292(17):7283-7284.
doi: 10.1074/jbc.H116.772434. Epub 2017 Apr 28.

Into the linker's DENN: A tyrosine's control of autophagy

Steve Caplan  1
Affiliations
Comment

Into the linker's DENN: A tyrosine's control of autophagy

Steve Caplan. J Biol Chem. .

Abstract

The small GTP-binding protein Rab12 plays an important role in the initiation of starvation-induced macroautophagy (autophagy) and is activated by the guanine-nucleotide exchange factor DENND3. However, the molecular mechanism by which DENND3 becomes activated has remained elusive. Xu and McPherson now identify a novel mechanism of DENND3 intramolecular binding that is regulated by the phosphorylation of a single tyrosine residue.

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Conflict of interest statement

The author declares that he has no conflicts of interest with the contents of this article

Figures

Figure 1.
Figure 1.
Proposed mechanism of DENND3 function in Rab12 activation. The evidence presented strongly supports the notion that DENND3 maintains an intramolecular interaction between Tyr940 of its linker region and the GTP exchange factor domain known as the DENN domain. By this model, phosphorylation of Tyr940, indicated by “P” surrounded by a red circle, relieves this intramolecular binding, altering the conformation to a more open structure and leading to enhanced DENN-domain GEF activity toward Rab12, which ultimately induces autophagy.
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