2 research outputs found
Different states of integrin LFA-1 aggregation are controlled through its association with tetraspanin CD9
This is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta - Mollecular Cell Research. A definitive version was subsequently published in Biochimica et Biophysica Acta - Mollecular Cell Research, 1853.10 (2015): 2464-2480 DOI: 10.1016/j.bbamcr.2015.05.018The tetraspanin CD9 has been shown to interact with different members of the β1 and
β3 subfamilies of integrins, regulating through these interactions cell adhesion,
migration and signaling. Based on confocal microscopy co-localization and on coimmunoprecipitation
results, we report here that CD9 associates with the β2 integrin
LFA-1 in different types of leukocytes including T, B and monocytic cells. This
association is resistant to stringent solubilisation conditions which, together with data
from chemical crosslinking, in situ Proximity Ligation Assays and pull-down
experiments, suggests a primary/direct type of interaction mediated by the Large
Extracellular Loop of the tetraspanin. CD9 exerts inhibitory effects on the adhesive
function of LFA-1 and on LFA-1-dependent leukocyte cytotoxic activity. The
mechanism responsible for this negative regulation exerted by CD9 on LFA-1 adhesion
does not involve changes in the affinity state of this integrin but seems to be related to
alterations in its state of aggregationThis work was supported by grant SAF2012-34561 from the Spanish «Ministerio de
Economía y Competitividad-MINECO», (to C.C.). R.R.M. salary is supported by a
«Profesor Ayudante» position from Departamento de Biología, Facutad de Ciencias,
Universidad Autónoma de Madri