Galectin-3 drives glycosphingolipid-dependent biogenesis of clathrin-independent carriers

Ramya Lakshminarayan, Christian Wunder, Ulrike Becken, Mark T. Howes, Carola Benzing, Senthil Arumugam, Susanne Sales, Nicholas Ariotti, Valérie Chambon, Christophe Lamaze, Damarys Loew, Andrej Shevchenko, Katharina Gaus, Robert G. Parton, Ludger Johannes

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160 Citations (Scopus)


Several cell surface molecules including signalling receptors are internalized by clathrin-independent endocytosis. How this process is initiated, how cargo proteins are sorted and membranes are bent remains unknown. Here, we found that a carbohydrate-binding protein, galectin-3 (Gal3), triggered the glycosphingolipid (GSL)-dependent biogenesis of a morphologically distinct class of endocytic structures, termed clathrin-independent carriers (CLICs). Super-resolution and reconstitution studies showed that Gal3 required GSLs for clustering and membrane bending. Gal3 interacted with a defined set of cargo proteins. Cellular uptake of the CLIC cargo CD44 was dependent on Gal3, GSLs and branched N-glycosylation. Endocytosis of Î 2 1-integrin was also reliant on Gal3. Analysis of different galectins revealed a distinct profile of cargoes and uptake structures, suggesting the existence of different CLIC populations. We conclude that Gal3 functionally integrates carbohydrate specificity on cargo proteins with the capacity of GSLs to drive clathrin-independent plasma membrane bending as a first step of CLIC biogenesis.

Original languageEnglish
Pages (from-to)592-603
Number of pages12
JournalNature Cell Biology
Issue number6
Publication statusPublished - Jun 2014
Externally publishedYes

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