Folliculin directs the formation of a Rab34-RILP complex to control the nutrient-dependent dynamic distribution of lysosomes

Georgina P Starling, Yan Y Yip, Anneri Sanger, Penny E Morton, Emily R Eden, Mark P Dodding

Research output: Contribution to journalArticle (Academic Journal)

248 Downloads (Pure)

Abstract

The spatial distribution of lysosomes is important for their function and is, in part, controlled by cellular nutrient status. Here, we show that the lysosome associated Birt-Hoge-Dubé (BHD) syndrome renal tumour suppressor folliculin (FLCN) regulates this process. FLCN promotes the peri-nuclear clustering of lysosomes following serum and amino acid withdrawal and is supported by the predominantly Golgi-associated small GTPase Rab34. Rab34-positive peri-nuclear membranes contact lysosomes and cause a reduction in lysosome motility and knockdown of FLCN inhibits Rab34-induced peri-nuclear lysosome clustering. FLCN interacts directly via its C-terminal DENN domain with the Rab34 effector RILP Using purified recombinant proteins, we show that the FLCN-DENN domain does not act as a GEF for Rab34, but rather, loads active Rab34 onto RILP We propose a model whereby starvation-induced FLCN association with lysosomes drives the formation of contact sites between lysosomes and Rab34-positive peri-nuclear membranes that restrict lysosome motility and thus promote their retention in this region of the cell.

Original languageEnglish
Pages (from-to)823-841
Number of pages19
JournalEMBO Reports
Volume17
Issue number6
Early online date13 Apr 2016
DOIs
Publication statusPublished - 1 Jun 2016

Bibliographical note

OA on VoR on publication. CC BY.

Keywords

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Line
  • Estrone
  • Gene Expression
  • Golgi Apparatus
  • Humans
  • Intracellular Membranes
  • Lysosomes
  • Protein Binding
  • Protein Transport
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Signal Transduction
  • Tumor Suppressor Proteins
  • rab GTP-Binding Proteins
  • Journal Article

Fingerprint Dive into the research topics of 'Folliculin directs the formation of a Rab34-RILP complex to control the nutrient-dependent dynamic distribution of lysosomes'. Together they form a unique fingerprint.

  • Cite this