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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number103809
Issue number2
StatePublished - 18 Feb 2022


FundersFunder number
Ethan Tyler
Fernström's Stiftelse
National Institute of Neurological Disorders and Stroke Intramural Research ProgramZIA NS003009-15, ZIA NS003105-10
Susan Cheng
National Institutes of Health
National Heart, Lung, and Blood InstituteISF-NSFC 2546/16
National Institute of Neurological Disorders and Stroke
Israel Science Foundation2141/20
Karolinska Institutet
Russian Science Foundation21-15-00227


    • Biological sciences
    • Cell biology
    • Endocrine regulation
    • Neuroscience


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