What is it about?

Endocytosis generates small vesicular cargoes that transport molecules from the surface into the cytoplasm of eukaryotic cells. Cargoes are involved in broad range of physiological processes, including nutrient uptake, cell signaling, recycling of plasma membrane components. Although several endocytic pathways have been described, clathrin-mediated endocytosis is the major endocytic route. More than fifty proteins are involved in the formation of endocytic clathrin-coated vesicles. The consecutive assembly of components of the clathrin machinery promotes the recruitment of cargoes as well as the induction of membrane curvature that result in the formation of an endocytic vesicle. In this work, we used innovative cell biology and live cell microscopy approaches to quantitatively investigate the role of the adaptor protein CALM, which is one of the key components of clathrin-coated vesicles.

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Why is it important?

We discovered that the adaptor CALM supports the formation of clathrin-coated vesicles by counteracting membrane tension. In particular, our experiments suggest that CALM promotes completion of the clathrin coated vesicle in a dose dependent manner. In other worlds, more CALM can be recruited to counteract membrane tension and internalize the vesicle. Since cells in our bodies experience membrane tension increase during embryogenesis, migration, or the late stages of cell cycle, and CALM expression varies across tissues, our results explain why CALM abrogation is lethal during development, or impair erythropoiesis.


We noticed that the region of Chromosome 11 that includes CALM gene is frequently amplified, together with its transcript in many tumor tissues, suggesting that CALM might improve the fitness of a specific subset of cancers.

Emanuele Cocucci
The Ohio State University

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This page is a summary of: CALM supports clathrin-coated vesicle completion upon membrane tension increase, Proceedings of the National Academy of Sciences, June 2021, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2010438118.
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