Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis
Autor/innen
- P. Moreno-Layseca
- N.Z. Jäntti
- R. Godbole
- C. Sommer
- G. Jacquemet
- H. Al-Akhrass
- J.R.W. Conway
- P. Kronqvist
- R.E. Kallionpää
- L. Oliveira-Ferrer
- P. Cervero
- S. Linder
- M. Aepfelbacher
- H. Zauber
- J. Rae
- R.G. Parton
- A. Disanza
- G. Scita
- S. Mayor
- M. Selbach
- S. Veltel
- J. Ivaska
Journal
- Nature Cell Biology
Quellenangabe
- Nat Cell Biol 23 (10): 1073-1084
Zusammenfassung
Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis and cancer invasion. Unlike cargo-specific clathrin-mediated endocytosis, the clathrin- and dynamin-independent endocytic pathway (CLIC-GEEC, CG pathway) is considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids. While the core molecular players of CG-endocytosis have been recently defined, evidence of cargo-specific adaptors or selective uptake of proteins for the pathway are lacking. Here we identify the actin-binding protein Swiprosin-1 (Swip1, EFHD2) as a cargo-specific adaptor for CG-endocytosis. Swip1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery - Arf1, IRSp53 and actin - and is critical for integrin endocytosis. Through this function, Swip1 supports integrin-dependent cancer-cell migration and invasion, and is a negative prognostic marker in breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG pathway and a role for specific adaptors in recruitment into this endocytic route.