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Cited by 55Cell Adhesion Molecules ResearchChemokine receptors and signalingCellular Mechanics and Interactions

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SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

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Pouwels, Jeroen, De Franceschi, Nicola, Rantakari, Pia, Auvinen, Kaisa, Karikoski, Marika, Mattila, Elina, Potter, Christopher, Sundberg, John P., Hogg, Nancy, Gahmberg, Carl G., Salmi, Marko, Ivaska, Johanna·2013·Cell Reports
DOI 10.1016/j.celrep.2013.10.011PMC PMC3852511
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Abstract

SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods) of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1), which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1), a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

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  • SHARPIN regulates cell adhesion and migration either by inhibition of integrins or by promotion of lamellipodium formation through the ARP2/3 complex.

    “What is known is that SHARPIN regulates cell adhesion and migration either by inhibition of integrins”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Pouwels et al., 2013

    The Results section ('SHARPIN Maintains LFA-1 in an Inactive Conformation and Regulates Lymphocyte Extravasation'; page not provided) reports that SHARPIN inhibits LFA-1 and affects lymphocyte adhesion and migration. Our copy does not support the additional claim that SHARPIN promotes lamellipodium formation through the ARP2/3 complex. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • SHARPIN is an important inactivator of integrins.

    “SHARPIN is also well known as an important inactivator of integrins”

    From SHARPIN S146 phosphorylation mediates ARP2/3 interaction, cancer cell invasion and metastasis (2022) · cites this paper as Pouwels, De Franceschi et al., 2013

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Metadata

Authors
Pouwels, J., De Franceschi, N., Rantakari, P., Auvinen, K., Karikoski, M., Mattila, E., Potter, C., Sundberg, J. P., Hogg, N., Gahmberg, C. G., Salmi, M., & Ivaska, J.
Affiliations
  • University of Turku (FI)
  • VTT Technical Research Centre of Finland (FI)
  • Jackson Laboratory (US)
  • Cancer Research UK (GB)
  • University of Helsinki (FI)
Corresponding author
Ivaska, Johanna
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2013-11
Volume
5
Issue
3
Pages
619-628
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2013.10.011
PMC
PMC3852511
OpenAlex
W1969660409
Cited by
55
References
1
Citations by year
2025: 1 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 11 · 2018: 2 · 2017: 6 · 2016: 3 · 2015: 7 · 2014: 2
FWCI
3.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Funders
  • Wellcome Trust
  • Finnish Cancer Institute
  • Cancer Research UK
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR49288, R01AR049288)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
SHARPIN, lymphocyte migration, LFA-1, ICAM-1, lymphocyte adhesion, cell polarization, migration speed, chronic inflammation
MeSH terms
Amino Acid Sequence, Animals, Carrier Proteins, Cell Adhesion, Cell Movement, Humans, Lymphocytes, Mice, Inbred C57BL, Molecular Sequence Data, Ubiquitins, Lymphocyte Function-Associated Antigen-1, Cell Polarity, Cell Surface Extensions, Intracellular Signaling Peptides and Proteins, Mice, HEK293 Cells

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