RESUMEN
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.
Asunto(s)
Proteínas del Citoesqueleto/metabolismo , Endocitosis/fisiología , Priones/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Membrana Celular , Proteínas del Citoesqueleto/genética , Citosol/fisiología , Regulación Fúngica de la Expresión Génica , Glutamina/química , Mecanotransducción Celular , Conformación Proteica , Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Sustancias ViscoelásticasRESUMEN
Colouterine fistulas are generally seen in post-menopausal patients and present with abdominal pain and non-physiologic vaginal drainage. A history of uterine pathology or diverticulitis is generally lacking. Visualization of the passage of contrast from the gastrointestinal tract to the uterus is not necessary to make the diagnosis. We present the case of a 44-year-old woman successfully treated for a colouterine fistula due to sigmoid diverticulitis. A variety of surgical approaches have been described to correct this fistula, and a minimally invasive colectomy without ileostomy or colostomy appears to be a safe approach.