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 language | English |
---|---|
Pages (from-to) | 823-841 |
Number of pages | 19 |
Journal | EMBO Reports |
Volume | 17 |
Issue number | 6 |
Early online date | 13 Apr 2016 |
DOIs | |
Publication status | Published - 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.Profiles
-
Professor Mark P Dodding
- School of Biochemistry - Professor of Molecular Cell Biology
Person: Academic