Self-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis

Yu, Y.; Ozaki, T.; Yoshimura, S. H.

doi:10.1101/2022.11.21.517438

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bioRxiv · 10.1101/2022.11.21.517438

Self-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis

Yu, Y.·Ozaki, T.·Yoshimura, S. H.

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Abstract

Clathrin-mediated endocytosis is pivotal to signal transduction pathways between the extracellular environment and the intracellular space. Evidence from live-cell imaging and super-resolution microscopy of mammalian cells suggests an asymmetric distribution of actin fibres near the clathrin-coated pit, which induces asymmetric pit-closing rather than radial constriction. However, detailed molecular mechanisms of this asymmetricity remain elusive. Herein, we used high-speed atomic force microscopy to demonstrate that CIP4, a multi-domain protein with a classic F-BAR domain and intrinsically disordered regions, is necessary for asymmetric pit-closing. Strong self-assembly of CIP4 via intrinsically disordered regions, together with stereospecific interactions with the curved membrane and actin-regulating proteins, generates a small actin-rich environment near the pit, which deforms the membrane and closes the pit. Our results provide mechanistic insights into how disordered and structured domain collaboration promotes spatio-temporal actin polymerisation near the plasma membrane.

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Yu, Y., Ozaki, T., Yoshimura, S. H.. 2022-11-22. Self-assembly of CIP4 drives actin-mediated asymmetric pit-closing in clathrin-mediated endocytosis. https://doi.org/10.1101/2022.11.21.517438

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