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

Abstract

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 clathrinmediated 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

Deciphering the Impact of PROM1 Alternative Splicing on Human Photoreceptor Development and Maturation

“…Our hypothesis is that endoA3 uptakes Prominin-1 from the cell surface during photoreceptors' development and once they mature, the interaction ceases, releasing Prominin-1 to the OSs, where it may play a role in OSs disk morphogenesis as highlighted by studies in Prom1-knockout mice 18,42 . Supporting this hypothesis, we found that the tumour marker CD166 is a clathrin-independent endocytosis cargo that is internalized in an endoA3-dependent manner 49,50 . As Prominin-1 and CD166…”

Distinct Bin/Amphiphysin/Rvs (BAR) family proteins may assemble on the same tubule to regulate membrane organization in vivo

“…Overall, the interplay between N-BAR and F-BAR proteins and their interaction with other cellular components form an intricate regulatory network that governs membrane dynamics, tubule formation, and actin regulation. These processes are essential for various cellular functions, including endocytosis, cell migration, and vesicular trafficking [ [26] , [27] , [28] ]. Previous findings suggest that N-BAR and F-BAR domain-containing proteins are segregated and localized to distinct tubules within the cells [ 22 ].…”

A CIE change in our understanding of endocytic mechanisms

“…Aside from these, new studies continue to reveal additional cargos that will likely allow us to better understand selection mechanisms during CME and CIE. For example, amyloid precursor protein (APP) and low-density lipoprotein internalize when clathrin and dynamin are inhibited, suggesting roles for an as-yet undetermined CIE route ( Aow et al, 2022 ). Similarly, uptake of L1CAM and CD166 through Endophilin-A3-mediated CIE may facilitate studies of pathways such as FEME or UFE ( Renard et al, 2019 ; Lemaigre et al, 2022 ).…”