Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis.
Title | Cargo-specific recruitment in clathrin- and dynamin-independent endocytosis. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Moreno-Layseca P, Jäntti NZ, Godbole R, Sommer C, Jacquemet G, Al-Akhrass H, Conway JRW, Kronqvist P, Kallionpää RE, Oliveira-Ferrer L, Cervero P, Linder S, Aepfelbacher M, Zauber H, Rae J, Parton RG, Disanza A, Scita G, Mayor S, Selbach M, Veltel S, Ivaska J |
Journal | Nat Cell Biol |
Date Published | 2021 Oct 06 |
ISSN | 1476-4679 |
Abstract | 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. |
DOI | 10.1038/s41556-021-00767-x |
Alternate Journal | Nat Cell Biol |
PubMed ID | 34616024 |
Grant List | 321493 / / Academy of Finland (Suomen Akatemia) / 325464 / / Academy of Finland (Suomen Akatemia) / 841973 / / EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Skłodowska-Curie Actions (H2020 Excellent Science - Marie Skłodowska-Curie Actions) / APP1140064 / / Department of Health | National Health and Medical Research Council (NHMRC) / VE 750/2-1 / / Deutsche Forschungsgemeinschaft (German Research Foundation) / 615258 / / EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) / |