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

• Published in: Traffic (Copenhagen, Denmark) Vol. 24; no. 4; pp. 190 - 212
• Main Authors: Lemaigre, Camille, Ceuppens, Apolline, Valades‐Cruz, Cesar Augusto, Ledoux, Benjamin, Vanbeneden, Bastien, Hassan, Mujtaba, Zetterberg, Fredrik R., Nilsson, Ulf J., Johannes, Ludger, Wunder, Christian, Renard, Henri‐François, Morsomme, Pierre
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01.04.2023; Wiley Subscription Services, Inc; Wiley
• Subjects: BAR domain proteins; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Biologi; Biological Sciences; Clathrin; Clathrin - metabolism; Clathrin‐independent endocytosis; Endocytosis; Endocytosis - physiology; endophilin‐A3; galectin; Galectins; Isoforms; L1CAM; Life Sciences; Metastases; Natural Sciences; Naturvetenskap; Nervous system; Neural Cell Adhesion Molecule L1; Protein Isoforms; PSTPIP1; endophilin-A3; PSTPIP1; BAR domain proteins; L1CAM; galectin; Clathrin-independent endocytosis
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/tra.12883

Recent 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. This study reveals that L1CAM is a clathrin‐independent cargo whose endocytosis is controlled by two BAR domain proteins, endophilin‐A3 and PSTPIP1. In addition, galectins regulate L1CAM internalisation.