Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis


  • 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


  • Nature Cell Biology


  • Nat Cell Biol 23 (10): 1073-1084


  • 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.