Endophilin-A3 and Galectin-8 control the clathrin-independent endocytosis of CD166.

Abstract	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.
Authors	Henri-François Renard, François Tyckaert, Cristina Lo Giudice, Thibault Hirsch, Cesar Augusto Valades-Cruz, Camille Lemaigre, Massiullah Shafaq-Zadah, Christian Wunder, Ruddy Wattiez, Ludger Johannes, Pierre van der Bruggen, David Alsteens, Pierre Morsomme
Journal	Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 1457 (03 19 2020) ISSN: 2041-1723 [Electronic] England
PMID	32193381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	ALCAM protein, human Adaptor Proteins, Signal Transducing Antigens, CD Cell Adhesion Molecules, Neuronal Clathrin Fetal Proteins Galectins LGALS8 protein, human RNA, Small Interfering Recombinant Proteins SH3GL3 protein, human
Topics	Adaptor Proteins, Signal Transducing (genetics, metabolism) Animals Antigens, CD (metabolism) Cell Adhesion Cell Adhesion Molecules, Neuronal (metabolism) Cell Line, Tumor Cell Membrane (metabolism) Cell Movement Chlorocebus aethiops Clathrin (metabolism) Endocytosis Fetal Proteins (metabolism) Fibroblasts Galectins (genetics, metabolism) Gene Knockdown Techniques Humans Intravital Microscopy Mice Neoplasms (pathology) RNA, Small Interfering Recombinant Proteins (genetics, metabolism)

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