Of condensates and coats - reciprocal regulation of clathrin assembly and the growth of protein networks

Brandon T. Malady, Andromachi Papagiannoula, Advika Kamatar, Susovan Sarkar, Gavin T. Lebrun, Liping Wang, Carl C. Hayden, Eileen M. Lafer, David J. Owen, Sigrid Milles () and Jeanne C. Stachowiak ()
Additional contact information
Brandon T. Malady: The University of Texas at Austin
Andromachi Papagiannoula: Leibniz-Forschungsinstitut für Molekulare Pharmakologie
Advika Kamatar: The University of Texas at Austin
Susovan Sarkar: The University of Texas at Austin
Gavin T. Lebrun: The University of Texas at Austin
Liping Wang: The University of Texas at San Antonio Health Science Center
Carl C. Hayden: The University of Texas at Austin
Eileen M. Lafer: The University of Texas at San Antonio Health Science Center
David J. Owen: University of Cambridge
Sigrid Milles: Leibniz-Forschungsinstitut für Molekulare Pharmakologie
Jeanne C. Stachowiak: The University of Texas at Austin

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Clathrin-mediated endocytosis is essential for membrane traffic, impacting a diverse range of cellular processes including cell signaling homeostasis, cell adhesion, and receptor recycling. During endocytosis, invagination of the plasma membrane is coordinated by a network of proteins that recruit and assemble the clathrin coat. Recent work demonstrated that clathrin accessory proteins which arrive early at endocytic sites, such as Eps15 and Fcho2, form phase-separated condensates that recruit downstream machinery, promoting maturation of clathrin-coated vesicles. However, the mechanisms by which protein condensates regulate and are regulated by clathrin assembly remain unclear. Using in vitro reconstitution and nuclear magnetic resonance spectroscopy, we demonstrate that protein condensates provide a platform for recruitment and assembly of clathrin triskelia. This condensate driven assembly is enhanced in the presence of the accessory protein, AP2, which is incorporated within condensates. In turn, clathrin assembly restricted condensate growth, exhibiting surfactant-like behavior that stabilized protein-protein interactions while imposing the preferred curvature of the clathrin lattice. This mutual regulation promotes assembly of clathrin-coated vesicles while preventing uncontrolled expansion of protein condensates. More broadly, reciprocal regulation of protein condensates and clathrin coats may provide a framework for understanding how disordered and structured protein assemblies can work together to build cellular architectures.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-64816-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64816-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-64816-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().