Related Experiment Video

Updated: May 30, 2026

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

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

Dirk Hubmacher1, Suneel S Apte

  • 1Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. hubmacd@ccf.org

Cellular and Molecular Life Sciences : CMLS
|August 23, 2011
PubMed

Insights

Mutations in fibrillin-1 (FBN1) and ADAMTS genes cause overlapping connective tissue disorders. Some ADAMTS proteins may regulate microfibril formation, impacting cell behavior.

Area of Science:

  • Connective tissue biology
  • Genetics of skeletal dysplasias
  • Extracellular matrix regulation

Background:

  • Fibrillin-1 is a key component of tissue microfibrils, regulating growth factor bioavailability and ocular zonule structure.
  • Mutations in FBN1 cause Marfan syndrome, Weill-Marchesani syndrome (WMS), isolated ectopia lentis (IEL), and geleophysic dysplasia (GD).
  • Interestingly, mutations in ADAMTS gene family members can phenocopy these FBN1-related disorders.

Purpose of the Study:

  • To explore the relationship between fibrillin-1 and ADAMTS gene mutations in connective tissue disorders.
  • To investigate the role of ADAMTS proteins in microfibril biogenesis and cell behavior.

Main Methods:

  • Comparative analysis of genetic mutations in FBN1 and ADAMTS gene families.
  • Review of clinical phenotypes associated with these mutations.
  • Examination of protein interactions between ADAMTS10, ADAMTSL2, and fibrillin-1.

Main Results:

  • Overlapping disease spectra observed for FBN1 and ADAMTS mutations, including WMS, IEL, and GD.
  • Identified interactions between ADAMTS10 and ADAMTSL2 with fibrillin-1.
  • Evidence suggests ADAMTS proteins accelerate microfibril biogenesis.

Conclusions:

  • The overlapping phenotypes suggest a functional link between fibrillin-1 and certain ADAMTS proteins.
  • Some ADAMTS proteins may have evolved to regulate microfibril formation through a novel mechanism.
  • This regulation of microfibril formation impacts downstream cell behavior.

More Related Videos

Using Microfluidics and Fluorescence Microscopy to Study the Assembly Dynamics of Single Actin Filaments and Bundles08:02

Using Microfluidics and Fluorescence Microscopy to Study the Assembly Dynamics of Single Actin Filaments and Bundles

Published on: May 5, 2022

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads07:55

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

Published on: March 8, 2017

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Cytoskeletal Accessory Proteins01:13

Cytoskeletal Accessory Proteins

The cytoskeleton is an essential cell component that plays several structural and functional roles. However, the filaments that make up the cytoskeleton cannot function independently and depend on the accessory or ancillary proteins to effectively carry out their function. Accessory proteins associate with cytoskeletal filaments and their monomers, aiding filament formation and function. They also help in the cross-communication among cytoskeletal filaments. Cytoskeletal accessory proteins are...
Formation of Higher-order Actin Filaments01:11

Formation of Higher-order Actin Filaments

The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin networks...
Fibril-associated Collagen01:11

Fibril-associated Collagen

Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Structural Protein Function01:56

Structural Protein Function

Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity.  In bones and teeth, it mineralizes to form...