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

2021; Nature Portfolio; Volume: 23; Issue: 10 Linguagem: Inglês

10.1038/s41556-021-00767-x

1476-4679

Paulina Moreno-Layseca, Niklas Z. Jäntti, Rashmi Godbole, Claudia Sommer, Guillaume Jacquemet, Hussein Al‐Akhrass, James R. W. Conway, Pauliina Kronqvist, Roosa Kallionpää, Leticia Oliveira‐Ferrer, 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,

Glycosylation and Glycoproteins Research

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.