Clathrin-mediated endocytosis cooperates with bulk endocytosis to generate vesicles
Gianvito Arpino,
Agila Somasundaram,
Wonchul Shin,
Lihao Ge,
Seth Villareal,
Chung Yu Chan,
Uri Ashery,
Oleg Shupliakov,
Justin W. Taraska,
Ling-Gang Wu
Affiliations
Gianvito Arpino
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Agila Somasundaram
National Heart, Lung, and Blood Institute, Bethesda, MD, USA
Wonchul Shin
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Lihao Ge
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Seth Villareal
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Chung Yu Chan
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA
Uri Ashery
Life Science Faculty, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
Oleg Shupliakov
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institute of Translational Biomedicine, St Petersburg State University, St Petersburg, Russia
Justin W. Taraska
National Heart, Lung, and Blood Institute, Bethesda, MD, USA; Corresponding author
Ling-Gang Wu
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Corresponding author
Summary: Clathrin-mediated endocytosis, the most prominent endocytic mode, is thought to be generated primarily from relatively flat patches of the plasma membrane. By employing conventional and platinum replica electron microscopy and super-resolution STED microscopy in neuroendocrine chromaffin cells, we found that large Ω-shaped or dome-shaped plasma membrane invaginations, previously thought of as the precursor of bulk endocytosis, are primary sites for clathrin-coated pit generation after depolarization. Clathrin-coated pits are more densely packed at invaginations rather than flat membranes, suggesting that invaginations are preferred sites for clathrin-coated pit formation, likely because their positive curvature facilitates coated-pit formation. Thus, clathrin-mediated endocytosis closely collaborates with bulk endocytosis to enhance endocytic capacity in active secretory cells. This direct collaboration between two classically independent endocytic pathways is of broad importance given the central role of both clathrin-mediated endocytosis and bulk endocytosis in neurons, endocrine cells, immune cells, and many other cell types throughout the body.
