The RAB GTPase RAB18 modulates macroautophagy and proteostasis

https://doi.org/10.1016/j.bbrc.2017.03.112Get rights and content
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Highlights

  • The RAB GTPase RAB18 is a positive modulator of macroautophagy.

  • The autophagy modulatory function of RAB18 is dependent on RAB3GAP1/2.

  • RAB18 is relevant for the maintenance of cellular proteostasis.

Abstract

Macroautophagy is a conserved degradative pathway and its deterioration is linked to disturbances in cellular proteostasis and multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy in primary human fibroblasts. The knockdown of RAB18 results in a decreased autophagic activity, while its overexpression enhances the degradative pathway. Importantly, this function of RAB18 is dependent on RAB3GAP1 and RAB3GAP2, which might act as RAB GEFs and stimulate the activity of the RAB GTPase. Moreover, the knockdown of RAB18 deteriorates proteostasis and results in the intracellular accumulation of ubiquitinated degradation-prone proteins. Thus, the RAB GTPase RAB18 is a positive modulator of autophagy and is relevant for the maintenance of cellular proteostasis.

Keywords

Autophagy
Proteostasis
RAB18
RAB3GAP1
RAB3GAP2
Warburg Micro syndrome

Abbreviations

ATG
autophagy related
cytoPrP
cytosolic prion protein
LC3
MAP1LC3
proteostasis
protein homeostasis
RAB18
member RAS oncogene
RAB GAP
RAB GTPase activating protein
RAB3GAP1/2
RAB3 GTPase activating protein subunit 1/2
RAB GEF
RAB guanine exchange factor
SQSTM1
sequestosome 1
WARBM
Warburg Micro syndrome

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