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bioRxiv · 10.1101/2022.07.29.502036

Dynein functions in galectin-3 mediated processes of clathrin-independent endocytosis

Mayya, C.·Naveena, H.·Sinha, P.·Bhatia, D. D.
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Abstract

Multiple endocytic processes operate in cells in tandem for the uptake of multiple cargoes, metabolites, and signaling molecules that are involved in diverse cellular functions including cell adhesion and migration. The best studied endocytic process involves the formation of a well-defined cytoplasmic coat at sites of uptake made of clathrin and its interacting partners. Galectin-3 (Gal3), an endogenous lectin, binds to glycosylated membrane receptors and glycosphingolipids (GSLs) to drive membrane bending, leading to the formation of tubular membrane invaginations which undergo scission to form a morphologically distinct class of uptake structures, termed clathrin-independent carriers (CLICs). This mechanism has been termed the GlycoLipid-Lectin (GL-Lect) hypothesis. Which components from cytoskeletal machinery are involved in the scission of CLICs remains yet to be explored. In this study, we propose that dynein, a retrograde motor protein, is recruited onto Gal3-induced tubular endocytic pits and provides the pulling force to for friction driven scission. Uptake of Gal3 and its cargoes (CD98/CD147) is significantly dependent on dynein activity, whereas the uptake of transferrin (a marker for clathrin-mediated endocytosis) is only slightly affected upon dynein inhibition. Dynein inhibition also affects cellular organelle distribution, 3D cell invasion and wound healing. Our study thereby reveals functions of dynein in individual and collective cell migration in 2D and 3D that are tightly coupled to endocytic processes in cells.

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Mayya, C., Naveena, H., Sinha, P., Bhatia, D. D.. 2022-07-29. Dynein functions in galectin-3 mediated processes of clathrin-independent endocytosis. https://doi.org/10.1101/2022.07.29.502036

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