PT  - JOURNAL ARTICLE
AU  - Paulina Moreno-Layseca
AU  - Niklas Z. Jäntti
AU  - Rashmi Godbole
AU  - Christian Sommer
AU  - Guillaume Jacquemet
AU  - Hussein Al-Akhrass
AU  - Pauliina Kronqvist
AU  - Roosa E. Kallionpää
AU  - Leticia Oliveira-Ferrer
AU  - Pasquale Cervero
AU  - Stefan Linder
AU  - Martin Aepfelbacher
AU  - James Rae
AU  - Robert G. Parton
AU  - Andrea Disanza
AU  - Giorgio Scita
AU  - Satyajit Mayor
AU  - Matthias Selbach
AU  - Stefan Veltel
AU  - Johanna Ivaska
TI  - Cargo-specific recruitment in clathrin and dynamin-independent endocytosis
AID  - 10.1101/2020.10.05.323295
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.05.323295
4099  - http://biorxiv.org/content/early/2020/10/05/2020.10.05.323295.short
4100  - http://biorxiv.org/content/early/2020/10/05/2020.10.05.323295.full
AB  - Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis, and cancer invasion and is often hijacked by viral infections 1. Unlike clathrin-mediated endocytosis, which exploits cargo-specific adaptors for selective protein internalization, the clathrin and dynamin-independent endocytic pathway (CLIC-GEEC, CG-pathway) has until now been considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids 2,3. Although the core molecular players of CG endocytosis have been recently defined, no cargo-specific adaptors are known and evidence of selective protein uptake into the pathway is lacking 3. Here, we identify the first cargo-specific adaptor for CG-endocytosis and demonstrate its clinical relevance in breast cancer progression. By combining unbiased molecular characterization and super-resolution imaging, we identified the actin-binding protein swiprosin-1 (EFHD2) as a cargo-specific adaptor regulating integrin internalization via the CG-pathway. Swiprosin-1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery, IRSp53 and actin. Swiprosin-1 is critical for integrin endocytosis, but not for other CG-cargo and supports integrin-dependent cancer cell migration and invasion, with clinically relevant implications for breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG-pathway and opens the possibility to discover more adaptors regulating it.Competing Interest StatementThe authors have declared no competing interest.