P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane

Nicola Hellen, Gregory I. Mashanov, Ianina L. Conte, Sophie le Trionnaire, Victor Babich, Laura Knipe, Alamin Mohammed, Kazim Ogmen, Silvia Martin-Almedina, Katalin Török, Matthew J. Hannah, Justin E. Molloy*, Tom Carter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
18 Downloads (Pure)

Abstract

In response to vascular damage, P-selectin molecules are secreted onto the surface of cells that line our blood vessels. They then serve as mechanical anchors to capture leucocytes from the blood stream. Here, we track individual P-selectin molecules released at the surface of live endothelial cells following stimulated secretion. We find P-selectin initially shows fast, unrestricted diffusion but within a few minutes, movement becomes increasingly restricted and ~50% of the molecules become completely immobile; a process similar to a sol-gel transition. We find removal of the extracellular C-type lectin domain (ΔCTLD) and/or intracellular cytoplasmic tail domain (ΔCT) has additive effects on diffusive motion while disruption of the adapter complex, AP2, or removal of cell-surface heparan sulphate restores mobility of full-length P-selectin close to that of ΔCT and ΔCTLD respectively. We have found P-selectin spreads rapidly from sites of exocytosis and evenly decorates the cell surface, but then becomes less mobile and better-suited to its mechanical anchoring function.

Original languageEnglish
Article number3031
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 31 May 2022

Bibliographical note

Funding Information: UK MRC program grant: MC_PC_13053 (T.C.), Francis Crick Institute core funding from Cancer Research UK: FC001119 (JEM), UK Medical Research Council: FC001119 (J.E.M.), Wellcome Trust: FC001119 (J.E.M.), BBSRC grant: BB/S003894/1 (K.T. and T.C.). We thank Ms. Ayoni Medagoda and Mr. Acieb Karasi for help with Cy3B labeling of AK6 and associated immunocytochemistry.

Open Access funding provided by The Francis Crick Institute.

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Publisher Copyright: © 2022, The Author(s).

Citation: Hellen, N., Mashanov, G.I., Conte, I.L. et al. P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane. Nat Commun 13, 3031 (2022). https://doi.org/10.1038/s41467-022-30669-x

DOI: https://doi.org/10.1038/s41467-022-30669-x

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