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

• DOI: 10.1038/s41556-021-00767-x
• Publication Date: 2021-10-07T08:22:58Z
• Authors: Paulina Moreno-La...; Niklas Z. Jäntti; Rashmi Godbole; Christian Sommer; Guillaume Jacquemet; Hussein Al-Akhrass; James R. W. Conway; Pauliina Kronqvist; Roosa E. Kallionpää; Leticia Oliveira-...; Pasquale Cervero; Stefan Linder; Martin Aepfelbacher; Henrik Zauber; James Rae; Robert G. Parton; Andrea Disanza; Giorgio Scita; Satyajit Mayor; Matthias Selbach; Stefan Veltel; Johanna Ivaska
• Keywords: Dynamins; 0303 health sciences; Integrin beta1; Intracellular Signaling Peptides and Proteins; Actins; Biological Transport; Breast Neoplasms; Cell Movement; Clathrin; Dynamins; Female; Humans; Integrin beta1; Intracellular Signaling Peptides and Proteins; rab GTP-Binding Proteins; Endocytosis; Biological Transport; Breast Neoplasms; ta3111; Actins; Clathrin; Endocytosis; 3. Good health; 03 medical and health sciences; Cell Movement; rab GTP-Binding Proteins; Humans; Female

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.