Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen
Summary Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collag...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
The Company of Biologists
2013-09-01
|
Series: | Biology Open |
Subjects: | |
Online Access: | http://bio.biologists.org/content/2/11/1148 |
id |
doaj-5401010204bf444e9e19d56465575104 |
---|---|
record_format |
Article |
spelling |
doaj-5401010204bf444e9e19d564655751042021-06-02T17:59:58ZengThe Company of BiologistsBiology Open2046-63902013-09-012111148115910.1242/bio.2013509020135090Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagenLisa A. Staudinger0Stephen J. Spano1Wilson Lee2Nuno Coelho3Dhaarmini Rajshankar4Michelle P. Bendeck5Tara Moriarty6Christopher A. McCulloch7 Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada Summary Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling.http://bio.biologists.org/content/2/11/1148Cell adhesionsMatrix remodelingPhagocytosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lisa A. Staudinger Stephen J. Spano Wilson Lee Nuno Coelho Dhaarmini Rajshankar Michelle P. Bendeck Tara Moriarty Christopher A. McCulloch |
spellingShingle |
Lisa A. Staudinger Stephen J. Spano Wilson Lee Nuno Coelho Dhaarmini Rajshankar Michelle P. Bendeck Tara Moriarty Christopher A. McCulloch Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen Biology Open Cell adhesions Matrix remodeling Phagocytosis |
author_facet |
Lisa A. Staudinger Stephen J. Spano Wilson Lee Nuno Coelho Dhaarmini Rajshankar Michelle P. Bendeck Tara Moriarty Christopher A. McCulloch |
author_sort |
Lisa A. Staudinger |
title |
Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen |
title_short |
Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen |
title_full |
Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen |
title_fullStr |
Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen |
title_full_unstemmed |
Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen |
title_sort |
interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2013-09-01 |
description |
Summary
Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling. |
topic |
Cell adhesions Matrix remodeling Phagocytosis |
url |
http://bio.biologists.org/content/2/11/1148 |
work_keys_str_mv |
AT lisaastaudinger interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen AT stephenjspano interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen AT wilsonlee interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen AT nunocoelho interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen AT dhaarminirajshankar interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen AT michellepbendeck interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen AT taramoriarty interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen AT christopheramcculloch interactionsbetweenthediscoidindomainreceptor1andb1integrinregulateattachmenttocollagen |
_version_ |
1721402398309613568 |