DOI: 10.1101/509133Dec 31, 2018Paper

A complex containing lysine-acetylated actin inhibits the formin INF2

BioRxiv : the Preprint Server for Biology
Mu AHenry N Higgs

Abstract

INF2 is a member of the formin family of actin assembly factors. Dominant mis-sense mutations in INF2 link to two diseases: focal segmental glomerulosclerosis (FSGS), a kidney disease; and Charcot-Marie-Tooth disease (CMTD), a neuropathy. All disease mutations map to the autoinhibitory Diaphanous Inhibitory Domain (DID). Curiously, purified INF2 is not autoinhibited, suggesting the existence of additional cellular inhibitors. We purified an INF2 inhibitor from mouse brain, and identified it as a complex between lysine-acetylated actin (KAc-actin) and cyclase-associated protein (CAP). Inhibition of INF2 by CAP/KAc-actin requires INF2 DID. Treatment of CAP/KAc-actin with histone deacetylase 6 (HDAC6) releases INF2 inhibition, while HDAC6 inhibitors block cellular INF2 activation. INF2 disease mutants are poorly inhibited by CAP/KAc-actin, suggesting that FSGS and CMTD result from reduced CAP/KAc-actin binding. This is the first demonstrated role for lysine-acetylated actin: regulation of an actin assembly factor by a novel mechanism, which we call facilitated auto-inhibition.

Related Concepts

Actins
Brain
Charcot-Marie-Tooth Disease
Focal Glomerulosclerosis
Metabolic Inhibition
Laboratory mice
Urologic Diseases
Formin 1
Inhibitors
Neuropathy

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

Journal of the Peripheral Nervous System : JPNS
Kentaro ToyotaKiyoshi Hayasaka
Pediatric Nephrology : Journal of the International Pediatric Nephrology Association
Patricia Q RodriguezJaakko Patrakka
Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
Gianluca CaridiGian Marco Ghiggeri
The New England Journal of Medicine
Olivia BoyerGéraldine Mollet
© 2021 Meta ULC. All rights reserved