Discoidin domain receptor 1 protein is a novel modulator of megakaryocyte-collagen interactions

Vittorio Abbonante, Cristian Gruppi, Diana Rubel, Oliver Gross, Remigio Moratti, Alessandra Balduini

Research output: Contribution to journalArticle

Abstract

Growing evidence demonstrates that extracellular matrices regulate many aspects of megakaryocyte (MK) development; however, among the different extracellular matrix receptors, integrin α2β1 and glycoprotein VI are the only collagen receptors studied in platelets and MKs. In this study, we demonstrate the expression of the novel collagen receptor discoidin domain receptor 1 (DDR1) by human MKs at both mRNA and protein levels and provide evidence of DDR1 involvement in the regulation of MK motility on type I collagen through a mechanism based on the activity of SHP1 phosphatase and spleen tyrosine kinase (Syk). Specifically, we demonstrated that inhibition of DDR1 binding to type I collagen, preserving the engagement of the other collagen receptors, glycoprotein VI, α2β1, and LAIR-1, determines a decrease in MK migration due to the reduction in SHP1 phosphatase activity and consequent increase in the phosphorylation level of its main substrate Syk. Consistently, inhibition of Syk activity restored MK migration on type I collagen. In conclusion, we report the expression and function of a novel collagen receptor on human MKs, and we point out that an increasing level of complexity is necessary to better understand MK-collagen interactions in the bone marrow environment.

Original languageEnglish
Pages (from-to)16738-16746
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number23
DOIs
Publication statusPublished - Jun 7 2013

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Abbonante, V., Gruppi, C., Rubel, D., Gross, O., Moratti, R., & Balduini, A. (2013). Discoidin domain receptor 1 protein is a novel modulator of megakaryocyte-collagen interactions. Journal of Biological Chemistry, 288(23), 16738-16746. https://doi.org/10.1074/jbc.M112.431528