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纤连蛋白协同位点可增强细胞黏附并介导整合素类别之间的相互作用。

The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes.

作者信息

Benito-Jardón Maria, Klapproth Sarah, Gimeno-LLuch Irene, Petzold Tobias, Bharadwaj Mitasha, Müller Daniel J, Zuchtriegel Gabriele, Reichel Christoph A, Costell Mercedes

机构信息

Department of Biochemistry and Molecular Biology, Universitat de València, Burjassot, Spain.

Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina, Universitat de València, Burjassot, Spain.

出版信息

Elife. 2017 Jan 16;6:e22264. doi: 10.7554/eLife.22264.

DOI:10.7554/eLife.22264
PMID:28092265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5279944/
Abstract

Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif () suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensable for the initial contact of α5β1 with the RGD, but essential to re-enforce the binding of α5β1/αIIbβ3 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when αvβ3 integrin levels decrease below a critical level.

摘要

纤连蛋白（FN）是细胞外基质的主要成分，可使整合素介导的细胞黏附，即α5β1、αIIbβ3和αv类整合素与RGD基序结合。α5和αIIb的另一个连接位点是位于RGD基序附近的协同位点。我们报道，具有功能失调的FN协同基序的小鼠，由于血管损伤后血栓形成延迟，血小板黏附及出血缺陷出人意料地轻微。β3整合素的进一步缺失会显著加重出血，并严重损害血管平滑肌细胞覆盖，导致胚胎致死。基于细胞的研究表明，协同位点对于α5β1与RGD的初始接触并非必需，但对于加强α5β1/αIIbβ3与FN的结合至关重要。我们的研究结果表明，当外力超过一定阈值或αvβ3整合素水平降至临界水平以下时，FN协同位点起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/da47198829ea/elife-22264-fig8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/d6f6a4067338/elife-22264-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/5c8ee96de33d/elife-22264-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/da47198829ea/elife-22264-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/7787b8a0837d/elife-22264-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/d58a746393b0/elife-22264-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/26b4ceb5e5dc/elife-22264-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/1eb36e43fe49/elife-22264-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/0780586bdf0a/elife-22264-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/cf6e1ae51ac2/elife-22264-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/126514c75518/elife-22264-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/65e0f20d2128/elife-22264-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/d47a195d7736/elife-22264-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/faff5034feb4/elife-22264-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/1badad7a2dad/elife-22264-fig5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5295/5279944/da47198829ea/elife-22264-fig8.jpg

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