Type I collagen fibrils and discoidin domain receptor 1 set invadosomes straight

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.

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Collagen and Discoidin Domain Receptor 1 Partnership: A Multifaceted Role in the Regulation of Breast Carcinoma Cell Phenotype

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.808625 ◽

2021 ◽

Vol 9 ◽

Author(s):

Charles Saby ◽

Erik Maquoi ◽

Frédéric Saltel ◽

Hamid Morjani

Keyword(s):

Cell Proliferation ◽

Breast Carcinoma ◽

Type I Collagen ◽

Carcinoma Cell ◽

Carcinoma Cells ◽

Type I ◽

Collagen Remodeling ◽

Breast Carcinoma Cells ◽

Discoidin Domain Receptor ◽

Discoidin Domain Receptor 1

Type I collagen, the major components of breast interstitial stroma, is able to regulate breast carcinoma cell behavior. Discoidin domain receptor 1 (DDR1) is a type I collagen receptor playing a key role in this process. In fact, collagen/DDR1 axis is able to trigger the downregulation of cell proliferation and the activation of BIK-mediated apoptosis pathway. The aim of this review is to discuss the role of two important factors that regulate these processes. The first factor is the level of DDR1 expression. DDR1 is highly expressed in epithelial-like breast carcinoma cells, but poorly in basal-like ones. Moreover, DDR1 undergoes cleavage by MT1-MMP, which is highly expressed in basal-like breast carcinoma cells. The second factor is type I collagen remodeling since DDR1 activation depends on its fibrillar organization. Collagen remodeling is involved in the regulation of cell proliferation and apoptosis through age- and proteolysis-related modifications.

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Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42–Tuba pathway

The Journal of Cell Biology ◽

10.1083/jcb.201404079 ◽

2014 ◽

Vol 207 (4) ◽

pp. 517-533 ◽

Cited By ~ 54

Author(s):

Amélie Juin ◽

Julie Di Martino ◽

Birgit Leitinger ◽

Elodie Henriet ◽

Anne-Sophie Gary ◽

...

Keyword(s):

Cell Invasion ◽

Type I Collagen ◽

Type I ◽

Dependent Manner ◽

Nucleotide Exchange ◽

Independent Manner ◽

Src Tyrosine Kinase ◽

Discoidin Domain Receptor ◽

Increased Risk ◽

Discoidin Domain Receptor 1

Accumulation of type I collagen fibrils in tumors is associated with an increased risk of metastasis. Invadosomes are F-actin structures able to degrade the extracellular matrix. We previously found that collagen I fibrils induced the formation of peculiar linear invadosomes in an unexpected integrin-independent manner. Here, we show that Discoidin Domain Receptor 1 (DDR1), a collagen receptor overexpressed in cancer, colocalizes with linear invadosomes in tumor cells and is required for their formation and matrix degradation ability. Unexpectedly, DDR1 kinase activity is not required for invadosome formation or activity, nor is Src tyrosine kinase. We show that the RhoGTPase Cdc42 is activated on collagen in a DDR1-dependent manner. Cdc42 and its specific guanine nucleotide-exchange factor (GEF), Tuba, localize to linear invadosomes, and both are required for linear invadosome formation. Finally, DDR1 depletion blocked cell invasion in a collagen gel. Altogether, our data uncover an important role for DDR1, acting through Tuba and Cdc42, in proteolysis-based cell invasion in a collagen-rich environment.

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Thermal (In)Stability of Type I Collagen Fibrils

Physical Review Letters ◽

10.1103/physrevlett.102.048101 ◽

2009 ◽

Vol 102 (4) ◽

Cited By ~ 6

Author(s):

S. G. Gevorkian ◽

A. E. Allahverdyan ◽

D. S. Gevorgyan ◽

A. L. Simonian

Keyword(s):

Type I Collagen ◽

Collagen Fibrils ◽

Type I

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Detection of type I collagen fibrils formation and dissociation by a fluorescence method based on thioflavin T

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2016.08.027 ◽

2016 ◽

Vol 92 ◽

pp. 1175-1182 ◽

Cited By ~ 11

Author(s):

Meilian Zou ◽

Huan Yang ◽

Haibo Wang ◽

Haiyin Wang ◽

Juntao Zhang ◽

...

Keyword(s):

Type I Collagen ◽

Collagen Fibrils ◽

Fluorescence Method ◽

Thioflavin T ◽

Type I

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Mechanical Properties of Native and Cross-linked Type I Collagen Fibrils

Biophysical Journal ◽

10.1529/biophysj.107.111013 ◽

2008 ◽

Vol 94 (6) ◽

pp. 2204-2211 ◽

Cited By ~ 126

Author(s):

Lanti Yang ◽

Kees O. van der Werf ◽

Carel F.C. Fitié ◽

Martin L. Bennink ◽

Pieter J. Dijkstra ◽

...

Keyword(s):

Mechanical Properties ◽

Type I Collagen ◽

Collagen Fibrils ◽

Type I

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Ultrastructural Study on the Specific Binding of Genetically Engineered Epidermal Growth Factor to Type I Collagen Fibrils

Bioconjugate Chemistry ◽

10.1021/bc700259g ◽

2007 ◽

Vol 18 (6) ◽

pp. 2137-2143 ◽

Cited By ~ 10

Author(s):

Koichi Kato ◽

Hideki Sato ◽

Hiroo Iwata

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Ultrastructural Study ◽

Type I Collagen ◽

Specific Binding ◽

Genetically Engineered ◽

Collagen Fibrils ◽

Type I ◽

Epidermal Growth

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The ultrastructure of type I collagen at nanoscale: large or small D-spacing distribution?

Nanoscale ◽

10.1039/c4nr01268b ◽

2014 ◽

Vol 6 (14) ◽

pp. 8134-8139 ◽

Cited By ~ 6

Author(s):

Hai-Nan Su ◽

Li-Yuan Ran ◽

Zhi-Hua Chen ◽

Qi-Long Qin ◽

Mei Shi ◽

...

Keyword(s):

Type I Collagen ◽

Collagen Fibrils ◽

Type I ◽

Spacing Distribution ◽

Large Distribution

The large distribution ofD-spacing values of type I collagen fibrils was due to image drift during measurement, and theD-spacing values were nearly identical both within a single fibril bundle and in different fibril bundles, exhibiting only a narrow distribution of 2.5 nm.

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Comparison of the Structural Characteristics of Native Collagen Fibrils Derived from Bovine Tendons Using Two Different Methods: Modified Acid-Solubilized and Pepsin-Aided Extraction

Materials ◽

10.3390/ma13020358 ◽

2020 ◽

Vol 13 (2) ◽

pp. 358 ◽

Cited By ~ 2

Author(s):

Haiyan Ju ◽

Xiuying Liu ◽

Gang Zhang ◽

Dezheng Liu ◽

Yongsheng Yang

Keyword(s):

Type I Collagen ◽

Structural Characteristics ◽

Polyacrylamide Gel Electrophoresis ◽

Sodium Dodecyl ◽

Dry Weight ◽

Collagen Fibrils ◽

Type I ◽

X Ray Diffraction ◽

Aggregation Structure ◽

Native Collagen

Native collagen fibrils (CF) were successfully extracted from bovine tendons using two different methods: modified acid-solubilized extraction for A-CF and pepsin-aided method for P-CF. The yields of A-CF and P-CF were up to 64.91% (±1.07% SD) and 56.78% (±1.22% SD) (dry weight basis), respectively. The analyses of both amino acid composition and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) confirmed that A-CF and P-CF were type I collagen fibrils. Both A-CF and P-CF retained the intact crystallinity and integrity of type I collagen’s natural structure by FTIR spectra, circular dichroism spectroscopy (CD) and X-ray diffraction detection. The aggregation structures of A-CF and P-CF were displayed by UV–Vis. However, A-CF showed more intact aggregation structure than P-CF. Microstructure and D-periodicities of A-CF and P-CF were observed (SEM and TEM). The diameters of A-CF and P-CF are about 386 and 282 nm, respectively. Although both A-CF and P-CF were theoretically concordant with the Schmitt hypothesis, A-CF was of evener thickness and higher integrity in terms of aggregation structure than P-CF. Modified acid-solubilized method provides a potential non-enzyme alternative to extract native collagen fibrils with uniform thickness and integral aggregation structure.

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