Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain.

Abstract:

:The endocytic and autophagic pathways are involved in the membrane trafficking of exogenous and endogenous materials to lysosomes. However, the mechanisms that regulate these pathways are largely unknown. We previously reported that Rubicon, a Beclin 1-binding protein, negatively regulates both the autophagic and endocytic pathways by unidentified mechanisms. In this study, we performed database searches to identify potential Rubicon homologues that share the common C-terminal domain, termed the RH domain. One of them, PLEKHM1, the causative gene of osteopetrosis, also suppresses endocytic transport but not autophagosome maturation. Rubicon and PLEKHM1 specifically and directly interact with Rab7 via their RH domain, and this interaction is critical for their function. Furthermore, we show that Rubicon but not PLEKHM1 uniquely regulates membrane trafficking via simultaneously binding both Rab7 and PI3-kinase.

journal_name

Mol Biol Cell

authors

Tabata K,Matsunaga K,Sakane A,Sasaki T,Noda T,Yoshimori T

doi

10.1091/mbc.E10-06-0495

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

4162-72

issue

23

eissn

1059-1524

issn

1939-4586

pii

E10-06-0495

journal_volume

21

pub_type

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