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HEMCAM/CD146 downregulates cell surface expression of beta1 integrins

Alais, S.
Allioli, N.
Pujades, C.
Duband, J. L.
Vainio, O.
Dunon, D.
Published in Journal of Cell Science. 2001, vol. 114, no. 10, p. 1847-1859
Abstract HEMCAM/gicerin, an immunoglobulin superfamily protein, is involved in homophilic and heterophilic adhesion. It interacts with NOF (neurite outgrowth factor), a molecule of the laminin family. Alternative splicing leads to mRNAs coding for HEMCAM with a short (HEMCAM-s) or a long cytoplasmic tail (HEMCAM-l). To investigate the cellular function of these two variants, we stably transfected murine fibroblasts with either form of HEMCAM. Expression of each isoform of this protein in L cells delayed proliferation and modified their adhesion properties to purified extracellular matrix proteins. Expression of either HEMCAM-s or HEMCAM-l inhibited integrin-dependent adhesion and spreading of fibroblasts to laminin 1, showing that this phenomenon did not depend on the cytoplasmic region. By contrast, L-cell adhesion and spreading to fibronectin depended on the HEMCAM isoform expressed. Flow cytometry and immunoprecipitation studies revealed that the expression of HEMCAM downregulated expression of the laminin-binding integrins alpha3beta1, alpha6beta1 and alpha7beta1, and fibronectin receptor alpha5beta1 from the cell surface. Semi-quantitative PCR and northern blot experiments showed that the expression of alpha6beta1 integrin modified by HEMCAM occurred at a translation or maturation level. Thus, our data demonstrate that HEMCAM regulates fibroblast adhesion by controlling beta1 integrin expression.
Keywords AnimalsAntigens, CDAntigens, CD146Antigens, CD29/ genetics/ metabolismAntigens, Surface/genetics/metabolismAvian ProteinsCell Adhesion/physiologyCell Adhesion Molecules/ genetics/ metabolismCell Division/physiologyCell Movement/physiologyCells, CulturedChick EmbryoDown-Regulation/physiologyFibroblasts/cytology/metabolismFlow CytometryGene Expression Regulation, DevelopmentalHumansIntegrin alpha6beta1Integrins/genetics/metabolismMembrane GlycoproteinsMembrane Proteins/genetics/metabolismMiceMolecular Sequence DataNeural Cell Adhesion MoleculesRNA, Messenger/analysisSequence Homology, Amino AcidTranscription, Genetic/physiologyTransfection
PMID: 11329371
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ALAIS, S. et al. HEMCAM/CD146 downregulates cell surface expression of beta1 integrins. In: Journal of Cell Science, 2001, vol. 114, n° 10, p. 1847-1859.

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Deposited on : 2010-08-27

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