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Cargo-specific recruitment in clathrin and dynamin-independent endocytosis

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Title:Cargo-specific recruitment in clathrin and dynamin-independent endocytosis
Creators Name:Moreno-Layseca, P. and Jäntti, N.Z. and Godbole, R. and Sommer, C. and Jacquemet, G. and Al-Akhrass, H. and Kronqvist, P. and Kallionpää, R.E. and Oliveira-Ferrer, L. and Cervero, P. and Linder, S. and Aepfelbacher, M. and Rae, J. and Parton, R.G. and Disanza, A. and Scita, G. and Mayor, S. and Selbach, M. and Veltel, S. and Ivaska, J.
Abstract:Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis, and cancer invasion and is often hijacked by viral infections. 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. 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. 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.
Keywords:Clathrin and Dynamin-Independent Endocytosis, Integrin, Swiprosin-1, Rab21, Breast Cancer
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.10.05.323295
Date:5 October 2020
Official Publication:https://doi.org/10.1101/2020.10.05.323295
Related to:
https://edoc.mdc-berlin.de/20978/Final version

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