Functional domains on elastin and microfibril-associated glycoprotein involved in elastic fibre assembly

BROWN-AUGSBURGER, P.; BROEKELMANN, T.; ROSENBLOOM, J.; MECHAM, R. P.

doi:10.1042/bj3230863u

Cited by 21 publications

(26 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16,17 FBN1, FBN2, ELN, MFAP1, MFAP2, MFAP3, and MFAP4 contribute to the biosynthesis of elastic fibers. 18 Metalloproteinases and their inhibitors influence the structure of the matrix. 19 For three loci that harbor four candidate genes (PLOD, FBLN2, COL16A1, and TIMP), we observed a perfect cosegregation of the hypothetical disease locus and the analyzed microsatellite markers.…”

Section: Discussionmentioning

confidence: 99%

Exclusion mapping of the genetic predisposition for cervical artery dissections by linkage analysis

Grond‐Ginsbach

Klima

Weber

et al. 2002

Annals of Neurology

View full text Add to dashboard Cite

Skin biopsies from a patient with a dissection of the left internal carotid artery and from four of his children were analyzed by electron microscopy. The index patient and three children showed mild but regular electron microscopic connective tissue aberrations. They were considered as carriers of an unknown autosomal dominant mutation. Thirty-four candidate genes involved in the biosynthesis of the extracellular matrix were excluded by genetic linkage analysis as possible sites of a disease-causing mutation in this family (logarithm of odds [LOD]-score less than -2.0).

show abstract

Section: Discussionmentioning

confidence: 99%

Exclusion mapping of the genetic predisposition for cervical artery dissections by linkage analysis

Grond‐Ginsbach

Klima

Weber

et al. 2002

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…MAGP-1 appears to be covalently bound to the microfibrils by intermolecular disulphide links71 72 and is also a substrate for transglutaminase,73 although it is not known which component of the microfibrils undergoes crosslinking with MAGP-1. Since the N-terminal region of MAGP-1 can undergo binding with both tropoelastin73 and type VI collagen,74 it is possible that MAGP-1 is responsible for the organisation of tropoelastin monomers in the ECM before cross linking,75 as well as playing a role in the interaction of fibrillin containing microfibrils and type VI collagen, which forms extensive networks of 3-5 nm microfibrils in virtually all soft connective tissues. MAGP-1 localises specifically to the “beads” of isolated microfibrils, and multiple MAGP-1 molecules may be present in a single bead 76…”

Section: Elastic Fibres Microfibrils and Fibrillinmentioning

confidence: 99%

The molecular genetics of Marfan syndrome and related microfibrillopathies

Robinson

Godfrey²

2000

Journal of Medical Genetics

257

160

View full text Add to dashboard Cite

Mutations in the gene for fibrillin-1 (FBN1) have been shown to cause Marfan syndrome, an autosomal dominant disorder of connective tissue characterised by pleiotropic manifestations involving primarily the ocular, skeletal, and cardiovascular systems. Fibrillin-1 is a major component of the 10-12 nm microfibrils, which are thought to play a role in tropoelastin deposition and elastic fibre formation in addition to possessing an anchoring function in some tissues.Fibrillin-1 mutations have also been found in patients who do not fulfil clinical criteria for the diagnosis of Marfan syndrome, but have related disorders of connective tissue, such as isolated ectopia lentis, familial aortic aneurysm, and Marfan-like skeletal abnormalities, so that Marfan syndrome may be regarded as one of a range of type 1 fibrillinopathies.There appear to be no particular hot spots since mutations are found throughout the entire fibrillin-1 gene. However, a clustering of mutations associated with the most severe form of Marfan syndrome, neonatal Marfan syndrome, has been noted in a region encompassing exons 24 to 32. The gene for fibrillin-2 (FBN2) is highly homologous to FBN1, and mutations in FBN2 have been shown to cause a phenotypically related disorder termed congenital contractural arachnodactyly. Since mutations in the fibrillin genes are likely to aVect the global function of the microfibrils, the term microfibrillopathy may be the most appropriate to designate the spectrum of disease associated with dysfunction of these molecules.The understanding of the global and the molecular functions of the fibrillin containing microfibrils is still incomplete and, correspondingly, no comprehensive theory of the pathogenesis of Marfan syndrome has emerged to date. Many, but not all, fibrillin-1 gene mutations are expected to exert a dominant negative eVect, whereby mutant fibrillin monomers impair the global function of the microfibrils. In this paper we review the molecular physiology and pathophysiology of Marfan syndrome and related microfibrillopathies. (J Med Genet 2000;37:9-25)

show abstract

“…In the blood vessel ECM where Egfl7 is located, MAGP‐1 is absent from endothelial connecting filaments but co‐localizes with the elastin‐associated microfibrils found in the vascular wall indicating that MAGP‐1 is ideally localized in order to support Egfl7 deposition in vivo . Furthermore, MAGP‐1 also interacts with tropoelastin and fibrillin 1 and 2 confirming its association with the elastic matrix. MAGP‐1 is not the only microfibrillar component that docks EGFL7 into the elastic ECM.…”

Section: Discussionmentioning

confidence: 76%

MAGP‐1 and fibronectin control EGFL7 functions by driving its deposition into distinct endothelial extracellular matrix locations

et al. 2018

View full text Add to dashboard Cite

The extracellular matrix (ECM) is essential to provide mechanical support to tissues but is also a bioactive edifice which controls cell behavior. Cell signaling generated by ECM components through integrin‐mediated contacts, modulates cell biological activity. In addition, by sequestrating or releasing growth factors, the ECM is an active player of physiological and pathological processes such as vascular development. EGFL7 is mainly expressed during blood vessel development and is deposited in the ECM after secretion by endothelial cells. While EGFL7 is known to control various endothelial cell molecular mechanisms [i.e., the repression of endothelial‐derived lysyl oxidase (LOX) enzyme, the regulation of the Notch pathway, and the expression of leukocyte adhesion molecules and of RHOA by endothelial cells], it is not established whether EGFL7 functions when bound to the ECM. Here, we show that microfibrillar‐associated glycoprotein‐1 (MAGP‐1) and fibronectin drive the deposition of EGFL7 into both fibers and individual aggregates in endothelial ECM. Although EGFL7 does not need to be docked into the ECM to control endothelial adhesion molecule expression, the ECM accumulation of EGFL7 is required for its regulation of LOX activity and of HEY2 expression along the Notch pathway. The interaction of EGFL7 with MAGP‐1 is necessary for LOX activity repression by EGFL7 while it does not participate in the control of the Notch pathway by this protein. Altogether, this study highlights the roles played by EGFL7 in controlling various endothelial molecular mechanisms upon its localization and shows how the ECM can modulate its functions.

show abstract

Functional domains on elastin and microfibril-associated glycoprotein involved in elastic fibre assembly

Cited by 21 publications

References 9 publications

Exclusion mapping of the genetic predisposition for cervical artery dissections by linkage analysis

Exclusion mapping of the genetic predisposition for cervical artery dissections by linkage analysis

The molecular genetics of Marfan syndrome and related microfibrillopathies

MAGP‐1 and fibronectin control EGFL7 functions by driving its deposition into distinct endothelial extracellular matrix locations

Contact Info

Product

Resources

About