A1 Refereed original research article in a scientific journal
Regulation of cell dynamics by rapid integrin transport through the biosynthetic pathway
Authors: Lerche, Martina; Mathieu, Mathilde; Hamidi, Hellyeh; Chastney, Megan; Jacquemet, Guillaume; Bruininks, Bart Marlon Herwig; Kaptan, Shreyas; Malerød, Lene; Pedersen, Nina Marie; Brech, Andreas; Matoba, Nobuyuki; Sato, Yuichiro; Vattulainen, Ilpo; Roca-Cusachs, Pere; Perez, Franck; Boncompain, Gaelle; Miserey, Stéphanie; Ivaska, Johanna
Publisher: Rockefeller University Press
Publication year: 2025
Journal: Journal of Cell Biology
Article number: e202508155
Volume: 225
Issue: 2
ISSN: 0021-9525
eISSN: 1540-8140
DOI: https://doi.org/10.1083/jcb.202508155
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://doi.org/10.1083/jcb.202508155
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/505798292
Constitutive integrin endocytosis and recycling control cell movement and morphology. In contrast, the role of newly synthesized integrins delivered via the biosynthetic pathway has been largely overlooked. We used the retention using selective hooks system to monitor the localization of new integrins exiting the endoplasmic reticulum in space and time. We discovered that new integrin delivery to the plasma membrane is polarized and enhances cell protrusion and focal adhesion growth in an extracellular matrix-ligand–dependent manner. Motor-clutch modeling explained the increased adhesion as higher integrin availability driving recruitment of additional receptors. Unexpectedly, live-cell imaging revealed a small subset of fast-emerging integrin vesicles rapidly transported to the cell surface to facilitate localized spreading. This unconventional secretion depended on cell adhesion and correlated with increased surface levels of immature, high-mannose glycosylated integrin, indicating bypass of the canonical Golgi-dependent secretory pathway. Thus, spatial plasma membrane-targeting of new integrins rapidly alters adhesion receptor availability, providing cells with added plasticity to respond to their environment.
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Funding information in the publication:
This study has been supported by the Finnish Cancer Institute (K. Albin Johansson Professorship Johanna Ivaska), the Research Council of Finland project (325464 Johanna Ivaska, 331349, 335527 Ilpo Vattulainen, 338537 Guillaume Jacquemet), and CoE in Biological Barrier Mechanics and Disease (346131 Johanna Ivaska, and 346135 Ilpo Vattulainen) funding, the Sigrid Juselius Foundation (Johanna Ivaska, Ilpo Vattulainen, Guillaume Jacquemet), the Finnish Cancer Organization (Johanna Ivaska, Guillaume Jacquemet), the Turku Doctoral Programme of Molecular Medicine (TuDMM; Martina Lerche), Svenska Kulturfonden (Martina Lerche), Victoriastiftelsen (Martina Lerche), K. Albin Johanssons Stiftelse (Martina Lerche), Marie Curie Skłodowska fellowship scheme (101033606 Shreyas Kaptan), Helsinki Institute of Life Science (HiLIFE) Fellow Program (Ilpo Vattulainen), Human Frontier Science Program (RGP0059/2019, Ilpo Vattulainen), the Åbo Akademi University Research Foundation (Guillaume Jacquemet, CoE CellMech), the Drug Discovery and Diagnostics strategic funding to Åbo Akademi University (Guillaume Jacquemet), EMBO (ALTF 798–2021 Mathilde Mathieu), the Foundation for the Finnish Cancer Institute (Mathilde Mathieu), a Research Council of Finland postdoctoral research grant (343239, Megan Chastney), the Norwegian Cancer Society (Nina Marie Pedersen), the Spanish Ministry of Science and Innovation (PID2022-142672NB-I00 to Pere Roca-Cusachs), the European Research Council (grant 101097753 MechanoSynth to Pere Roca-Cusachs), and the prize “ICREA Academia” for excellence in research (Pere Roca-Cusachs). IBEC is a recipient of a Severo Ochoa Award of Excellence from the Spanish Ministry of Science and Innovation.
