UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Burns SO, Killock DJ, Moulding DA, Metelo J, Nunes J, Taylor RR, Forge A, Thrasher AJ, Ivetic A
  • Publication date:
    01/07/2010
  • Pagination:
    5355, 5365
  • Journal:
    Blood
  • Volume:
    115
  • Issue:
    26
  • Status:
    Published
  • Country:
    United States
  • PII:
    S0006-4971(20)58384-5
  • Language:
    eng
  • Keywords:
    Actins, Cell Adhesion, Cell Line, Tumor, Cell Membrane, Cells, Cultured, Gene Expression, Genetic Diseases, X-Linked, Humans, L-Selectin, Leukocytes, Mononuclear, Leukopenia, Lymphocytes, Microvilli, Mutation, Wiskott-Aldrich Syndrome Protein
Abstract
Leukocytes rely on dynamic actin-dependent changes in cell shape to pass through blood vessels, which is fundamental to immune surveillance. Wiskott-Aldrich Syndrome protein (WASp) is a hematopoietic cell-restricted cytoskeletal regulator important for modulating cell shape through Arp2/3-mediated actin polymerization. A recently identified WASp(I294T) mutation was shown to render WASp constitutively active in vivo, causing increased filamentous (F)-actin polymerization, high podosome turnover in macrophages, and myelodysplasia. The aim of this study was to determine the effect of WASp(I294T) expression in lymphocytes. Here, we report that lymphocytes isolated from a patient with WASp(I294T), and in a cellular model of WASp(I294T), displayed abnormal microvillar architecture, associated with an increase in total cellular F-actin. Microvillus function was additionally altered as lymphocytes bearing the WASp(I294T) mutation failed to roll normally on L-selectin ligand under flow. This was not because of defects in L-selectin expression, shedding, cytoskeletal anchorage, or membranal positioning; however, under static conditions of adhesion, WASp(I294T)-expressing lymphocytes exhibited altered dynamic interaction with L-selectin ligand, with a significantly reduced rate of adhesion turnover. Together, our results demonstrate that WASp(I294T) significantly affects lymphocyte membrane topography and L-selectin-dependent adhesion, which may be linked to defective hematopoiesis and leukocyte function in affected patients.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Div of Infection & Immunity
Author
The Ear Institute
Author
Developmental Biology & Cancer Dept
Author
Infection, Immunity & Inflammation Dept
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by