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



: Moreno-Layseca Paulina, Jäntti Niklas Z, Godbole Rashmi, Sommer Christian, Jacquemet Guillaume, Al-Akhrass Hussein, Conway James RW, Kronqvist Pauliina, Kallionpää Roosa E, Oliveira-Ferrer Leticia, Cervero Pasquale, Linder Stefan, Aepfelbacher Martin, Zauber Henrik, Rae James, Parton Robert G, Disanza Andrea, Scita Giorgio, Mayor Satyajit, Selbach Matthias, Veltel Stefan, Ivaska Johanna

Publisher: NATURE PORTFOLIO

: 2021

: Nature Cell Biology

: NATURE CELL BIOLOGY

: NAT CELL BIOL

: 23

: 10

: 1073

: 1084

: 40

: 1465-7392

: 1476-4679

DOI: https://doi.org/10.1038/s41556-021-00767-x(external)

: https://research.utu.fi/converis/portal/detail/Publication/67555401(external)


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.Moreno-Layseca et al. identify Swip1 as an integrin-specific endocytic adaptor controlling the dynamics of integrin adhesion complexes as well as the migration and invasion of breast cancer cells.

Last updated on 2024-26-11 at 13:14