RNF167 targets Arl8B for degradation to regulate lysosome positioning and endocytic trafficking

Rakesh Deshar, Song Moon, Wonjin Yoo, Eun Bee Cho, Sungjoo K. Yoon, Jong Bok Yoon

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The protease-associated (PA) domain-containing E3 ubiquitin ligases are transmembrane proteins located in intracellular organelles such as the endoplasmic reticulum, endosomes, or lysosomes. The functional roles of these ubiquitin ligases are not well defined. To understand the function of E3 ubiquitin ligases, identification of their substrates is of critical importance. In this study, we describe a newly devised method based on proximity-dependent biotin labeling to identify substrates of ubiquitin ligases. Application of this method to RING finger protein 167 (RNF167), a member of the PA domain-containing E3 family, led to identification of Arl8B as its substrate. We demonstrated that RNF167 ubiquitinates Arl8B at the lysine residue K141 and reduces the level of the Arl8B protein. Overexpression and knockdown of RNF167 revealed its regulatory role in Arl8B-dependent lysosome positioning and endocytic trafficking to lysosomes. Furthermore, we found that the ubiquitination-defective Arl8B K141R mutant counteracts RNF167 in these cellular events. These results indicate that RNF167 plays a crucial role as an E3 ubiquitin ligase targeting Arl8B to regulate lysosome positioning and endocytic trafficking.

Original languageEnglish
Pages (from-to)4583-4599
Number of pages17
JournalFEBS Journal
Volume283
Issue number24
DOIs
Publication statusPublished - 2016 Dec 1

Bibliographical note

Funding Information:
We thank Dr Michael B. Brenner (Harvard University, Cambridge, MA, USA) for his gift of anti-Arl8B antibodies. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2012R1A1A2043191 and 2015R1D1A1A2061749).

Publisher Copyright:
© 2016 Federation of European Biochemical Societies

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'RNF167 targets Arl8B for degradation to regulate lysosome positioning and endocytic trafficking'. Together they form a unique fingerprint.

Cite this