title: Discoidin domain receptor 1 protein is a novel modulator of megakaryocyte-collagen interactions.
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.
authors.affiliation: Biotechnology Research Laboratories, Department of Molecular Medicine, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Matteo Foundation, University of Pavia, 27100 Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Abbonante
authors.affiliation: Biotechnology Research Laboratories, Department of Molecular Medicine, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Matteo Foundation, University of Pavia, 27100 Pavia, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Gruppi
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Rubel
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gross
authors.affiliation: Biotechnology Research Laboratories, Department of Molecular Medicine, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Matteo Foundation, University of Pavia, 27100 Pavia, Italy.
authors.forename: Remigio
authors.initials: R
authors.lastname: Moratti
authors.affiliation: Biotechnology Research Laboratories, Department of Molecular Medicine, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) San Matteo Foundation, University of Pavia, 27100 Pavia, Italy; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155. Electronic address: alessandra.balduini@unipv.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Balduini
mesh_terms: D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D000070819:Discoidin Domain Receptor 1; D005260:Female; D006801:Humans; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000201:enzymology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000072377:Syk Kinase
chemical_list: D018955:CD36 Antigens; D024042:Collagen Type I; D038982:Integrin alpha2beta1; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6
keywords: Bone Marrow; Discoidin Domain Receptor 1; Extracellular Matrix; Hematopoiesis; Megakaryocytes; Phosphatase; Receptors