Abnormal expression of proteoglycans in Ullrich's disease with collagen VI deficiency

Higashi, Keiko; Higuchi, Itsuro; Niiyama, Takahito; Uchida, Youhei; Shiraishi, Tadafumi; Hashiguchi, Akihiro; Saito, Akiko; Horikiri, Takashi; Suehara, Masahito; Arimura, Kimiyoshi; Osame, Mitsuhiro

doi:10.1002/mus.20449

Cited by 12 publications

(7 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, although we used the monomeric α1(V)-N-propeptide in our initial Y2H screen, we show by our solid phase binding assay that the heterotrimeric type V collagen interacts with type VI collagen, thereby supporting the interaction of type VI collagen with the physiological form of type V collagen. Previously, type VI collagen was shown to interact with various ECM components including type I, II, IV, and XIV collagens, FN, fibromodulin, hyaluronic acid, perlecan, decorin, biglycan, tenascin-X and cell receptors such as the integrins and the NG2 transmembrane proteoglycan [33]. Type VI collagen is widely distributed in connective tissues and particularly abundant in the pericellular environment, where it functions to anchor the basement membrane to the underlying connective tissue [31].…”

Section: Resultsmentioning

confidence: 99%

Identification of binding partners interacting with the α1-N-propeptide of type V collagen

Symoens

Renard

Bonod‐Bidaud

et al. 2010

Biochemical Journal

View full text Add to dashboard Cite

The predominant form of type V collagen is the [α1(V)]₂α2(V) heterotrimer. Mutations in COL5A1 or COL5A2, encoding respectively the α1(V)- and α2(V)-collagen chain, cause classic EDS (Ehlers-Danlos syndrome), a heritable connective tissue disorder, characterized by fragile hyperextensible skin and joint hypermobility. Approximately half of the classic EDS cases remain unexplained. Type V collagen controls collagen fibrillogenesis through its conserved α1(V)-N-propeptide domain. To gain an insight into the role of this domain, a yeast two-hybrid screen among proteins expressed in human dermal fibroblasts was performed utilizing the N-propeptide as a bait. We identified 12 interacting proteins, including extracellular matrix proteins and proteins involved in collagen biosynthesis. Eleven interactions were confirmed by surface plasmon resonance and/or co-immunoprecipitation: α1(I)- and α2(I)-collagen chains, α1(VI)-, α2(VI)- and α3(VI)-collagen chains, tenascin-C, fibronectin, PCPE-1 (procollagen C-proteinase enhancer-1), TIMP-1 (tissue inhibitor of metalloproteinases-1), MMP-2 (matrix metalloproteinase 2) and TGF-β1 (transforming growth factor β1). Solid-phase binding assays confirmed the involvement of the α1(V)-N-propeptide in the interaction between native type V collagen and type VI collagen, suggesting a bridging function of this protein complex in the cell-matrix environment. Enzymatic studies showed that processing of the α1(V)-N-propeptide by BMP-1 (bone morphogenetic protein 1)/procollagen C-proteinase is enhanced by PCPE-1. These interactions are likely to be involved in extracellular matrix homoeostasis and their disruption could explain the pathogenetic mechanism in unresolved classic EDS cases.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of binding partners interacting with the α1-N-propeptide of type V collagen

Symoens

Renard

Bonod‐Bidaud

et al. 2010

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Ten possible candidate genes were considered on the basis of the following criteria: either i) their direct interaction with collagen VI, as in the case of HSPG2 [13], ITGA1, ITGA2, ITGB1 [14], DNC and BGN [15]; ii) their secondary involvement in collagen VI-deficient tissues, as in NG2-proteoglycan [16,17], ITGA5 and ITGA7 [18,19], or iii) their mutations causing an overlapping phenotype with collagen VI-related myopathies, as in TNXB [20]. COL6A5 (COL29A1) and COL6A6, which are expressed in skeletal muscle, were also included since collagen VI alpha1-deficient mice do not express collagen VI alpha 5 or alpha 6 chains [21].…”

Section: Resultsmentioning

confidence: 99%

Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies

et al. 2010

View full text Add to dashboard Cite

BackgroundMolecular characterization of collagen-VI related myopathies currently relies on standard sequencing, which yields a detection rate approximating 75-79% in Ullrich congenital muscular dystrophy (UCMD) and 60-65% in Bethlem myopathy (BM) patients as PCR-based techniques tend to miss gross genomic rearrangements as well as copy number variations (CNVs) in both the coding sequence and intronic regions.MethodsWe have designed a custom oligonucleotide CGH array in order to investigate the presence of CNVs in the coding and non-coding regions of COL6A1, A2, A3, A5 and A6 genes and a group of genes functionally related to collagen VI. A cohort of 12 patients with UCMD/BM negative at sequencing analysis and 2 subjects carrying a single COL6 mutation whose clinical phenotype was not explicable by inheritance were selected and the occurrence of allelic and genetic heterogeneity explored.ResultsA deletion within intron 1A of the COL6A2 gene, occurring in compound heterozygosity with a small deletion in exon 28, previously detected by routine sequencing, was identified in a BM patient. RNA studies showed monoallelic transcription of the COL6A2 gene, thus elucidating the functional effect of the intronic deletion. No pathogenic mutations were identified in the remaining analyzed patients, either within COL6A genes, or in genes functionally related to collagen VI.ConclusionsOur custom CGH array may represent a useful complementary diagnostic tool, especially in recessive forms of the disease, when only one mutant allele is detected by standard sequencing. The intronic deletion we identified represents the first example of a pure intronic mutation in COL6A genes.

show abstract

“…Fibroblasts are commonly used for functional studies of muscular dystrophy and have resulted in better understanding of several muscle diseases such as distal myopathy with rimmed vacuoles, muscle–eye‐brain disease and Emery–Dreifuss muscular dystrophy to name a few (35–38). Moreover, dysferlin trafficking and the effect of caveolin‐3 disease mutations on this process in muscle cells can be recapitulated in the fibroblasts (31).…”

Section: Resultsmentioning

confidence: 99%

Patients with a Non‐dysferlin Miyoshi Myopathy have a Novel Membrane Repair Defect

Jaiswal

Marlow

Summerill

et al. 2006

Traffic

View full text Add to dashboard Cite

Two autosomal recessive muscle diseases, limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), are caused by mutations in the dysferlin gene. These mutations result in poor ability to repair cell membrane damage, which is suggested to be the cause for this disease. However, many patients who share clinical features with MM‐type muscular dystrophy do not carry mutations in dysferlin gene. To understand the basis of MM that is not due to mutations in dysferlin gene, we analyzed cells from patients in one such family. In these patients, we found no defects in several potential candidates – annexin A2, caveolin‐3, myoferlin and the MMD2 locus on chromosome 10p. Similar to dysferlinopathy, these cells also exhibit membrane repair defects and the severity of the defect correlated with severity of their disease. However, unlike dysferlinopathy, none of the conventional membrane repair pathways are defective in these patient cells. These results add to the existing evidence that cell membrane repair defect may be responsible for MM‐type muscular dystrophy and indicate that a previously unsuspected genetic lesion that affects cell membrane repair pathway is responsible for the disease in the non‐dysferlin MM patients.

show abstract

Abnormal expression of proteoglycans in Ullrich's disease with collagen VI deficiency

Cited by 12 publications

References 37 publications

Identification of binding partners interacting with the α1-N-propeptide of type V collagen

Identification of binding partners interacting with the α1-N-propeptide of type V collagen

Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies

Patients with a Non‐dysferlin Miyoshi Myopathy have a Novel Membrane Repair Defect

Contact Info

Product

Resources

About