Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function

Multi-author review

DOI: 10.1007/s00018-011-0780-9

Cite this article as:
Hubmacher, D. & Apte, S.S. Cell. Mol. Life Sci. (2011) 68: 3137. doi:10.1007/s00018-011-0780-9

Summary

Tissue microfibrils contain fibrillin-1 as a major constituent. Microfibrils regulate bioavailability of TGFβ superfamily growth factors and are structurally crucial in the ocular zonule. FBN1 mutations typically cause the Marfan syndrome, an autosomal dominant disorder manifesting with skeletal overgrowth, aortic aneurysm, and lens dislocation (ectopia lentis). Infrequently, FBN1 mutations cause dominantly inherited Weill–Marchesani syndrome (WMS), isolated ectopia lentis (IEL), or the fibrotic condition, geleophysic dysplasia (GD). Intriguingly, mutations in ADAMTS [a disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif] family members phenocopy these disorders, leading to recessive WMS (ADAMTS10), WMS-like syndrome (ADAMTS17), IEL (ADAMTSL4 and ADAMTS17) and GD (ADAMTSL2). An ADAMTSL2 founder mutation causes Musladin–Lueke syndrome, a fibrotic disorder in beagle dogs. The overlapping disease spectra resulting from fibrillin-1 and ADAMTS mutations, interaction of ADAMTS10 and ADAMTSL2 with fibrillin-1, and evidence that these ADAMTS proteins accelerate microfibril biogenesis, constitutes a consilience suggesting that some ADAMTS proteins evolved to provide a novel mechanism regulating microfibril formation and consequently cell behavior.

Keywords

Fibrillin ADAMTS Marfan syndrome Weill–Marchesani syndrome Ectopia lentis Fibrosis Scleroderma 

Abbreviations

ADAMTS

A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type-1 motif

ECM

Extracellular matrix

GD

Geleophysic dysplasia

HSPG

Heparan sulfate proteoglycan

IEL

Isolated ectopia lentis

MFS

Marfan syndrome

MIM

Mendelian inheritance in man

MLS

Musladin–Lueke syndrome

TGFβ

Transforming growth factor β

WMS

Weill–Marchesani syndrome

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Biomedical Engineering, Lerner Research InstituteCleveland ClinicClevelandUSA
  2. 2.Department of Biomedical Engineering-ND20Cleveland ClinicClevelandUSA

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