2. Academic Validation
  3. Reticular adhesions are assembled at flat clathrin lattices and opposed by active integrin α5β1

Reticular adhesions are assembled at flat clathrin lattices and opposed by active integrin α5β1

  • J Cell Biol. 2023 Aug 7;222(8):e202303107. doi: 10.1083/jcb.202303107.
Laura Hakanpää 1 2 3,  Amr Abouelezz 1 2 3,  An-Sofie Lenaerts 1 2 3,  Seyda Culfa 1 2 3,  Michael Algie 1 2,  Jenny Bärlund 1 2 3,  Pekka Katajisto 1 2 3 4,  Harvey McMahon 5,  Leonardo Almeida-Souza 1 2 3
Affiliations

Affiliations

  • 1 Helsinki Institute of Life Science, University of Helsinki , Helsinki, Finland.
  • 2 Institute of Biotechnology, University of Helsinki , Helsinki, Finland.
  • 3 Faculty of Biological and Environmental Sciences, University of Helsinki , Helsinki, Finland.
  • 4 Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
  • 5 MRC Laboratory of Molecular Biology , Cambridge, UK.
PMID: 37233325 DOI: 10.1083/jcb.202303107
Abstract

Reticular adhesions (Ras) consist of Integrin αvβ5 and harbor flat clathrin lattices (FCLs), long-lasting structures with similar molecular composition as clathrin-mediated endocytosis (CME) carriers. Why FCLs and Ras colocalize is not known. Here, we show that Ras are assembled at FCLs in a process controlled by fibronectin (FN) and its receptor, Integrin α5β1. We observed that cells on FN-rich matrices displayed fewer FCLs and Ras. CME machinery inhibition abolished Ras and live-cell imaging showed that RA establishment requires FCL coassembly. The inhibitory activity of FN was mediated by the activation of Integrin α5β1 at Tensin1-positive fibrillar adhesions. Conventionally, endocytosis disassembles cellular adhesions by internalizing their components. Our results present a novel paradigm in the relationship between these two processes by showing that endocytic proteins can actively function in the assembly of cell adhesions. Furthermore, we show this novel adhesion assembly mechanism is coupled to cell migration via unique crosstalk between cell-matrix adhesions.

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