While several clathrin-independent endocytic processes have been described so far, their biological relevance often remains elusive, especially in pathophysiological contexts such as cancer. In this ...study, we find that the tumor marker CD166/ALCAM (Activated Leukocyte Cell Adhesion Molecule) is a clathrin-independent cargo. We show that endophilin-A3-but neither A1 nor A2 isoforms-functionally associates with CD166-containing early endocytic carriers and physically interacts with the cargo. Our data further demonstrates that the three endophilin-A isoforms control the uptake of distinct subsets of cargoes. In addition, we provide strong evidence that the construction of endocytic sites from which CD166 is taken up in an endophilin-A3-dependent manner is driven by extracellular galectin-8. Taken together, our data reveal the existence of a previously uncharacterized clathrin-independent endocytic modality, that modulates the abundance of CD166 at the cell surface, and regulates adhesive and migratory properties of cancer cells.
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.
Les bibliothèques sont-elles un lieu d’archivage, et si c’est le cas, qu’archivent-elles et comment le font-elles ? Cet ouvrage discute la pertinence des frontières convenues entre archives et ...bibliothèques, et examine dans la longue durée la construction des lieux de conservation documentaire et des fonctions, tantôt bien distinctes, tantôt plus hybrides, qui leur sont attribuées par les sociétés européennes. À partir d’études de cas, ce volume retrace les circonstances dans lesquelles certains types de documents ont été considérés comme des archives et comment ils ont été répartis dans les dépôts d’archives ou dans les bibliothèques. Il examine les critères qui fondent cette distinction institutionnelle et documentaire, et la manière dont ces choix ont conditionné le travail de tri, de sélection, de classement, de description et de consultation. Il invite ainsi à réexaminer la genèse des fonds documentaires, au sein des familles, des institutions de l’État ou des cabinets d’érudits, et à comprendre autrement les conditions documentaires de la fabrique de l’histoire, hier et aujourd’hui.
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