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Sandeep Kumar

Alumni

Publications

Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling
Louis-Philippe Bergeron-Sandoval
Sandeep Kumar
Hossein Khadivi Heris
Catherine L. A. Chang
Caitlin E. Cornell
Sarah L. Keller
Paul François
Adam G. Hendricks
Allen J. Ehrlicher
Rohit V. Pappu
Stephen W. Michnick
Significance The uptake of molecules into cells, known as endocytosis, requires membrane invagination and the formation of vesicles. A versi… (see more)on of endocytosis that is independent of actin polymerization is aided by the assembly of membraneless biomolecular condensates at the site of membrane invagination. Here, we show that endocytic condensates are viscoelastic bodies that concentrate key proteins with prion-like domains to enable membrane remodeling. A distinct molecular grammar, namely the preference for glutamine versus asparagine residues, underlies the cohesive interactions that give rise to endocytic condensates. We incorporate material properties inferred using active rheology into a mechanical model to explain how cohesive interactions within condensates and interfacial tensions among condensates, membranes, and the cytosol can drive membrane invagination to initiate endocyosis. Membrane invagination and vesicle formation are key steps in endocytosis and cellular trafficking. Here, we show that endocytic coat proteins with prion-like domains (PLDs) form hemispherical puncta in the budding yeast, Saccharomyces cerevisiae. These puncta have the hallmarks of biomolecular condensates and organize proteins at the membrane for actin-dependent endocytosis. They also enable membrane remodeling to drive actin-independent endocytosis. The puncta, which we refer to as endocytic condensates, form and dissolve reversibly in response to changes in temperature and solution conditions. We find that endocytic condensates are organized around dynamic protein–protein interaction networks, which involve interactions among PLDs with high glutamine contents. The endocytic coat protein Sla1 is at the hub of the protein–protein interaction network. Using active rheology, we inferred the material properties of endocytic condensates. These experiments show that endocytic condensates are akin to viscoelastic materials. We use these characterizations to estimate the interfacial tension between endocytic condensates and their surroundings. We then adapt the physics of contact mechanics, specifically modifications of Hertz theory, to develop a quantitative framework for describing how interfacial tensions among condensates, the membrane, and the cytosol can deform the plasma membrane to enable actin-independent endocytosis.
2021-12-09
Proceedings of the National Academy of Sciences of the United States of America (published)
doi.org