en
Scientific article
Open access
English

HEMCAM/CD146 downregulates cell surface expression of beta1 integrins

Published inJournal of cell science, vol. 114, no. 10, p. 1847-1859
Publication date2001
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
  • Animals
  • Antigens, CD
  • Antigens, CD146
  • Antigens, CD29/ genetics/ metabolism
  • Antigens, Surface/genetics/metabolism
  • Avian Proteins
  • Cell Adhesion/physiology
  • Cell Adhesion Molecules/ genetics/ metabolism
  • Cell Division/physiology
  • Cell Movement/physiology
  • Cells, Cultured
  • Chick Embryo
  • Down-Regulation/physiology
  • Fibroblasts/cytology/metabolism
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Humans
  • Integrin alpha6beta1
  • Integrins/genetics/metabolism
  • Membrane Glycoproteins
  • Membrane Proteins/genetics/metabolism
  • Mice
  • Molecular Sequence Data
  • Neural Cell Adhesion Molecules
  • RNA, Messenger/analysis
  • Sequence Homology, Amino Acid
  • Transcription, Genetic/physiology
  • Transfection
Affiliation Not a UNIGE publication
Citation (ISO format)
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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accessLevelPublic
Identifiers
ISSN of the journal0021-9533
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