Journal of Biological Chemistry
Volume 288, Issue 36, 6 September 2013, Pages 26147-26156
Journal home page for Journal of Biological Chemistry

Cell Biology
Relief of Autoinhibition Enhances Vta1 Activation of Vps4 via the Vps4 Stimulatory Element*

https://doi.org/10.1074/jbc.M113.494112Get rights and content
Under a Creative Commons license
open access

The endosomal sorting complexes required for transport (ESCRTs) impact multiple cellular processes including multivesicular body sorting, abscission, and viral budding. The AAA-ATPase Vps4 is required for ESCRT function, and its full activity is dependent upon the co-factor Vta1. The Vta1 carboxyl-terminal Vta1 SBP1 Lip5 (VSL) domain stimulates Vps4 function by facilitating oligomerization of Vps4 into its active state. Here we report the identification of the Vps4 stimulatory element (VSE) within Vta1 that is required for additional stimulation of Vps4 activity in vitro and in vivo. VSE activity is autoinhibited in a manner dependent upon the unstructured linker region joining the amino-terminal microtubule interacting and trafficking domains and the carboxyl-terminal VSL domain. The VSE is also required for Vta1-mediated Vps4 stimulation by ESCRT-III subunits Vps60 and Did2. These results suggest that ESCRT-III binding to the Vta1 microtubule interacting and trafficking domains relieves linker region autoinhibition of the VSE to produce maximal activation of Vps4 during ESCRT function.

Background: Vta1 promotes Vps4 ATPase activity and facilitates ESCRT-III stimulation of Vps4.

Results: The Vta1 VSE (Vps4 stimulatory element) mediates ESCRT-III-enhanced activation of Vps4 and contributes to Vta1 function in vivo.

Conclusion: ESCRT-III binding Vta1 relieves autoinhibition of the VSE to promote activation of Vps4.

Significance: These studies identify a novel mechanism whereby ESCRT-III and Vta1 regulate Vps4 activity.

ATPases
Endosomes
Protein Sorting
Protein Turnover
Receptor Endocytosis
AAA-ATPase
ESCRT
Vps4
Vta1
Multivesicular Body

Cited by (0)

*

This work was supported, in whole or in part, by National Institutes of Health Grant R01 GM73024 (to A. P. N) and National Institutes of Health F30 Predoctoral Fellowship 1F30DA26762 (to A. P. N.). This work was also supported by American Heart Association Predoctoral Fellowship 09PRE2220147 (to A. P. N.), the Mayo Graduate School (to A. P. N.), and a Fraternal Order of the Eagles postdoctoral fellowship (to B. A. D.).

This article contains supplemental Figs. 1 and 2.

1

Both authors contributed equally to this work.

2

Present address: Dept. of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.