N‐BAR and F‐BAR proteins—endophilin‐A3 and PSTPIP1—control clathrin‐independent endocytosis of L1CAM

Author:

Lemaigre Camille1ORCID,Ceuppens Apolline1,Valades‐Cruz Cesar Augusto234,Ledoux Benjamin1,Vanbeneden Bastien1,Hassan Mujtaba5,Zetterberg Fredrik R.6,Nilsson Ulf J.5,Johannes Ludger2,Wunder Christian2,Renard Henri‐François7ORCID,Morsomme Pierre1ORCID

Affiliation:

1. UCLouvain, Louvain Institute of Biomolecular Science and Technology Group of Molecular Physiology Louvain‐la‐Neuve Belgium

2. Institut Curie, Université PSL, U1143 INSERM, UMR3666 CNRS, Cellular and Chemical Biology unit Paris France

3. SERPICO Project Team, UMR144 CNRS Institut Curie PSL Research University Paris France

4. SERPICO Project Team, Inria Centre Rennes‐Bretagne Atlantique Campus Universitaire de Beaulieu Rennes France

5. Department of Chemistry Lund University Lund Sweden

6. Galecto Biotech AB Sahlgrenska Science Park Gothenburg Sweden

7. UNamur, NARILIS Unité de recherche en biologie cellulaire animale (URBC) Namur Belgium

Abstract

AbstractRecent advances in the field demonstrate the high diversity and complexity of endocytic pathways. In the current study, we focus on the endocytosis of L1CAM. This glycoprotein plays a major role in the development of the nervous system, and is involved in cancer development and is associated with metastases and poor prognosis. Two L1CAM isoforms are subject to endocytosis: isoform 1, described as a clathrin‐mediated cargo; isoform 2, whose endocytosis has never been studied. Deciphering the molecular machinery of isoform 2 internalisation should contribute to a better understanding of its pathophysiological role. First, we demonstrated in our cellular context that both isoforms of L1CAM are mainly a clathrin‐independent cargo, which was not expected for isoform 1. Second, the mechanism of L1CAM endocytosis is specifically mediated by the N‐BAR domain protein endophilin‐A3. Third, we discovered PSTPIP1, an F‐BAR domain protein, as a novel actor in this endocytic process. Finally, we identified galectins as endocytic partners and negative regulators of L1CAM endocytosis. In summary, the interplay of the BAR proteins endophilin‐A3 and PSTPIP1, and galectins fine tune the clathrin‐independent endocytosis of L1CAM.

Funder

Agence Nationale de la Recherche

Publisher

Wiley

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology

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