The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways

Andrea Gubas, Christina Karantanou, Doris Popovic, Georg Tascher, Marina E. Hoffmann, Anna Platzek, Nina Dawe, Ivan Dikic (Lead / Corresponding author), Daniela S. Krause (Lead / Corresponding author), David G. McEwan (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
44 Downloads (Pure)

Abstract

The lysosome is a cellular signalling hub at the point of convergence of endocytic and autophagic pathways, where the contents are degraded and recycled. Pleckstrin homology domain-containing family member 1 (PLEKHM1) acts as an adaptor to facilitate the fusion of endocytic and autophagic vesicles with the lysosome. However, it is unclear how PLEKHM1 function at the lysosome is controlled. Herein, we show that PLEKHM1 co-precipitates with, and is directly phosphorylated by, mTOR. Using a phospho-specific antibody against Ser432/S435 of PLEKHM1, we show that the same motif is a direct target for ERK2-mediated phosphorylation in a growth factor-dependent manner. This dual regulation of PLEKHM1 at a highly conserved region points to a convergence of both growth factor- and amino acid-sensing pathways, placing PLEKHM1 at a critical juncture of cellular metabolism.

Original languageEnglish
Pages (from-to)864-880
Number of pages17
JournalFEBS Letters
Volume595
Issue number7
Early online date16 Jan 2021
DOIs
Publication statusPublished - Apr 2021

Fingerprint

Dive into the research topics of 'The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways'. Together they form a unique fingerprint.

Cite this