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

Vittorio Abbonante1, Cristian Gruppi1, Diana Rubel2

  • 1Biotechnology Research Laboratories, Department of Molecular Medicine, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Matteo Foundation, University of Pavia, 27100 Pavia, Italy.

The Journal of Biological Chemistry
|March 27, 2013
PubMed

Insights

Human megakaryocytes (MKs) express a novel collagen receptor, discoidin domain receptor 1 (DDR1). DDR1 regulates MK motility on collagen via SHP1 phosphatase and spleen tyrosine kinase (Syk) pathways.

Area of Science:

  • Hematology
  • Cell Biology
  • Biochemistry

Background:

  • Extracellular matrices critically influence megakaryocyte (MK) development.
  • Integrin α2β1 and glycoprotein VI are known collagen receptors in MKs and platelets.
  • The role of other collagen receptors in MK function remains largely unexplored.

Purpose of the Study:

  • To investigate the expression and function of discoidin domain receptor 1 (DDR1) as a novel collagen receptor in human MKs.
  • To elucidate the signaling pathway involving DDR1 in regulating MK motility on type I collagen.

Main Methods:

  • Demonstration of DDR1 mRNA and protein expression in human MKs.
  • Assessment of MK migration on type I collagen with DDR1 inhibition.
  • Analysis of SHP1 phosphatase activity and Syk phosphorylation levels.

Main Results:

  • Human MKs express DDR1 at both mRNA and protein levels.
  • Inhibition of DDR1-collagen interaction reduced MK migration by decreasing SHP1 activity and increasing Syk phosphorylation.
  • Restoration of MK migration was observed upon Syk inhibition.

Conclusions:

  • Discoidin domain receptor 1 (DDR1) is a novel functional collagen receptor on human megakaryocytes.
  • DDR1 regulates MK motility through a pathway involving SHP1 phosphatase and spleen tyrosine kinase (Syk).
  • Understanding MK-collagen interactions requires further investigation into complex signaling networks within the bone marrow.
Keywords:
Bone MarrowDiscoidin Domain Receptor 1Extracellular MatrixHematopoiesisMegakaryocytesPhosphataseReceptors

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