Evaluated: The Sec7 Arf-GEF Is Recruited to the trans-Golgi Network by Positive Feedback.

Another Faculty of 1000 evaluation:

The Sec7 Arf-GEF Is Recruited to the trans-Golgi Network by Positive Feedback.

BC Richardson, CM McDonold, JC Fromme

Developmental Cell 2012 vol. 22 4

PMID: 22516198 DOI: 10.1016/j.devcel.2012.02.006

This paper sheds light on the complex issues of both how and where Arf proteins are activated. Here, the authors show that the Sec7 Arf-guanine nucleotide exchange factor (GEF) from yeast (Saccharomyces cerevisiae) is recruited by its own product, activated Arf1, in a positive feedback loop. This suggests a means by which sustained activation can be achieved. Importantly the data are also consistent with models where Sec7 exists in an autoinhibited state that requires activation to drive guanine nucleotide exchange on Arf1. The HDS1 domain of Sec7 acts as a switch controlling activation where membrane association is the trigger for that switch. Arf1 interacts with the HDS1 domain to recruit Sec7 to membranes and this same domain is then required for subsequent rounds of Arf1 activation. The HDS1 domain also appears to play a key role in targeting Sec7 to the trans-Golgi network in S. cerevisiae. The authors propose that it is not recruited by Arf1 located at other parts of the Golgi because it is out-competed by COPI. Alternatively, one could envisage additional factors driving selective recruitment.

The principles defined for Arf1/Sec7 here have been shown previously to apply to other systems such as that of ARNO {1}. This work provides a substantial framework for analysis of the more complex situation in metazoans, notably mammals.


{1} Stalder D, Barelli H, Gautier R, Macia E, Jackson CL, Antonny B (2011) Kinetic studies of the Arf activator Arno on model membranes in the presence of Arf effectors suggest control by a positive feedback loop. J Biol Chem 286(5): 3873-83