NDLI: Collagen VI Microfibril Formation Is Abolished by an α2(VI) von Willebrand Factor Type A Domain Mutation in a Patient with Ullrich Congenital Muscular Dystrophy*

Content Provider	PubMed Central
Author	Tooley, Leona D. Zamurs, Laura K. Beecher, Nicola Baker, Naomi L. Peat, Rachel A. Adams, Naomi E. Bateman, John F. North, Kathryn N. Baldock, Clair Lamandé, Shireen R.
Abstract	Collagen VI is an extracellular protein that most often contains the three genetically distinct polypeptide chains, α1(VI), α2(VI), and α3(VI), although three recently identified chains, α4(VI), α5(VI), and α6(VI), may replace α3(VI) in some situations. Each chain has a triple helix flanked by N- and C-terminal globular domains that share homology with the von Willebrand factor type A (VWA) domains. During biosynthesis, the three chains come together to form triple helical monomers, which then assemble into dimers and tetramers. Tetramers are secreted from the cell and align end-to-end to form microfibrils. The precise molecular mechanisms responsible for assembly are unclear. Mutations in the three collagen VI genes can disrupt collagen VI biosynthesis and matrix organization and are the cause of the inherited disorders Bethlem myopathy and Ullrich congenital muscular dystrophy. We have identified a Ullrich congenital muscular dystrophy patient with compound heterozygous mutations in α2(VI). The first mutation causes skipping of exon 24, and the mRNA is degraded by nonsense-mediated decay. The second mutation is a two-amino acid deletion in the C1 VWA domain. Recombinant C1 domains containing the deletion are insoluble and retained intracellularly, indicating that the mutation has detrimental effects on domain folding and structure. Despite this, mutant α2(VI) chains retain the ability to associate into monomers, dimers, and tetramers. However, we show that secreted mutant tetramers containing structurally abnormal C1 VWA domains are unable to associate further into microfibrils, directly demonstrating the critical importance of a correctly folded α2(VI) C1 domain in microfibril formation.
Related Links	http://dx.doi.org/10.1074/jbc.m110.152520
Ending Page	33576
Page Count	10
Starting Page	33567
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	43
Volume Number	285
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-10-22
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Collagen VI Microfibril Formation Is Abolished by an α2(VI) von Willebrand Factor Type A Domain Mutation in a Patient with Ullrich Congenital Muscular Dystrophy

Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

Ullrich congenital muscular dystrophy and bethlem myopathy: clinical and genetic heterogeneity

Exome sequencing identified a novel Col6α1 mutation in an Iranian patient with Ullrich congenital muscular dystrophy: a case report

Tendon Extracellular Matrix Alterations in Ullrich Congenital Muscular Dystrophy

Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy

The N-terminal N5 Subdomain of the α3(VI) Chain Is Important for Collagen VI Microfibril Formation

Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice

A novel variant in the COL6A1 gene causing Ullrich congenital muscular dystrophy in a consanguineous family: a case report

Collagen VI Microfibril Formation Is Abolished by an α2(VI) von Willebrand Factor Type A Domain Mutation in a Patient with Ullrich Congenital Muscular Dystrophy*

Similar Documents

Collagen VI Microfibril Formation Is Abolished by an α2(VI) von Willebrand Factor Type A Domain Mutation in a Patient with Ullrich Congenital Muscular Dystrophy

Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

Ullrich congenital muscular dystrophy and bethlem myopathy: clinical and genetic heterogeneity

Exome sequencing identified a novel Col6α1 mutation in an Iranian patient with Ullrich congenital muscular dystrophy: a case report

Tendon Extracellular Matrix Alterations in Ullrich Congenital Muscular Dystrophy

Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy

The N-terminal N5 Subdomain of the α3(VI) Chain Is Important for Collagen VI Microfibril Formation

Collagen-VI supplementation by cell transplantation improves muscle regeneration in Ullrich congenital muscular dystrophy model mice

A novel variant in the COL6A1 gene causing Ullrich congenital muscular dystrophy in a consanguineous family: a case report

Collagen VI Microfibril Formation Is Abolished by an α2(VI) von Willebrand Factor Type A Domain Mutation in a Patient with Ullrich Congenital Muscular Dystrophy*