Talk:Extracellular Matrix 1
- 1 2017
- 2 2016
Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone
Semin Cell Dev Biol. 2017 Feb;62:142-151. doi: 10.1016/j.semcdb.2016.11.005. Epub 2016 Nov 9.
Ito S1, Nagata K2. Author information
Abstract Hsp47, a collagen-specific molecular chaperone that localizes in the endoplasmic reticulum (ER), is indispensable for molecular maturation of collagen. Hsp47, which is encoded by the SERPINH1 gene, belongs to the serpin family and has the serpin fold; however, it has no serine protease inhibitory activity. Hsp47 transiently binds to procollagen in the ER, dissociates in the cis-Golgi or ER-Golgi intermediate compartment (ERGIC) in a pH-dependent manner, and is then transported back to the ER via its RDEL retention sequence. Hsp47 recognizes collagenous (Gly-Xaa-Arg) repeats on triple-helical procollagen and can prevent local unfolding and/or aggregate formation of procollagen. Gene disruption of Hsp47 in mice causes embryonic lethality due to impairments in basement membrane and collagen fibril formation. In Hsp47-knockout cells, the type I collagen triple helix forms abnormally, resulting in thin and frequently branched fibrils. Secretion of type I collagens is slow and plausible in making aggregates of procollagens in the ER of hsp47-knocked out fibroblasts, which are ultimately degraded by autophagy. Mutations in Hsp47 are causally associated with osteogenesis imperfecta. Expression of Hsp47 is strongly correlated with expression of collagens in multiple types of cells and tissues. Therefore, Hsp47 represents a promising target for treatment of collagen-related disorders, including fibrosis of the liver, lung, and other organs. Copyright © 2016 Elsevier Ltd. All rights reserved. KEYWORDS: Collagen; Fibrosis; Heat-shock protein; Molecular chaperone; Osteogenesis imperfecta; Serpin
Adhesion protein networks reveal functions proximal and distal to cell-matrix contacts
Curr Opin Cell Biol. 2016 Apr;39:93-100. doi: 10.1016/j.ceb.2016.02.013. Epub 2016 Feb 27.
Byron A1, Frame MC2. Author information Abstract Cell adhesion to the extracellular matrix is generally mediated by integrin receptors, which bind to intracellular adhesion proteins that form multi-molecular scaffolding and signalling complexes. The networks of proteins, and their interactions, are dynamic, mechanosensitive and extremely complex. Recent efforts to characterise adhesions using a variety of technologies, including imaging, proteomics and bioinformatics, have provided new insights into their composition, organisation and how they are regulated, and have also begun to reveal unexpected roles for so-called adhesion proteins in other cellular compartments (for example, the nucleus or centrosomes) in diseases such as cancer. We believe this is opening a new chapter on understanding the wider functions of adhesion proteins, both proximal and distal to cell-matrix contacts. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved. PMID 26930633
Matrix metalloproteinase interactions with collagen and elastin
Matrix Biol. 2015 Jan 17. pii: S0945-053X(15)00006-2. doi: 10.1016/j.matbio.2015.01.005. [Epub ahead of print] Van Doren SR1.
Abstract Most abundant in the extracellular matrix are collagens, joined by elastin that confers elastic recoil to the lung, aorta, and skin. These fibrils are highly resistant to proteolysis but can succumb to a minority of the matrix metalloproteinases (MMPs). Considerable inroads to understanding how such MMPs move to the susceptible sites in collagen and then unwind the triple helix of collagen monomers have been gained. The essential role in unwinding of the hemopexin-like domain of interstitial collagenases or the collagen binding domain of gelatinases is highlighted. Elastolysis is also facilitated by the collagen binding domain in the cases of MMP-2 and MMP-9, and remote exosites of the catalytic domain in the case of MMP-12. Copyright © 2015. Published by Elsevier B.V. KEYWORDS: Collagen triple helix; Elastin; Exosite; Matrix metalloproteinases PMID 25599938
The evolution of metazoan extracellular matrix
The fibrillar collagen family
Int J Mol Sci. 2010 Jan 28;11(2):407-26.
Exposito JY, Valcourt U, Cluzel C, Lethias C.
Institut de Biologie et Chimie des Protéines, CNRS UMR, Université de Lyon, France. firstname.lastname@example.org <email@example.com>
Collagens, or more precisely collagen-based extracellular matrices, are often considered as a metazoan hallmark. Among the collagens, fibrillar collagens are present from sponges to humans, and are involved in the formation of the well-known striated fibrils. In this review we discuss the different steps in the evolution of this protein family, from the formation of an ancestral fibrillar collagen gene to the formation of different clades. Genomic data from the choanoflagellate (sister group of Metazoa) Monosiga brevicollis, and from diploblast animals, have suggested that the formation of an ancestral alpha chain occurred before the metazoan radiation. Phylogenetic studies have suggested an early emergence of the three clades that were first described in mammals. Hence the duplication events leading to the formation of the A, B and C clades occurred before the eumetazoan radiation. Another important event has been the two rounds of "whole genome duplication" leading to the amplification of fibrillar collagen gene numbers, and the importance of this diversification in developmental processes. We will also discuss some other aspects of fibrillar collagen evolution such as the development of the molecular mechanisms involved in the formation of procollagen molecules and of striated fibrils.
PMID: 20386646 http://www.ncbi.nlm.nih.gov/pubmed/20386646
Collagen Type VI-Related Disorders
Lampe AK, Flanigan KM, Bushby KM. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-. 2004 Jun 25 [updated 2007 Apr 06].
Excerpt Disease characteristics. Collagen type VI-related disorders include Bethlem myopathy and Ullrich congenital muscular dystrophy (CMD). Bethlem myopathy is characterized by the combination of proximal muscle weakness and variable contractures, affecting most frequently the long finger flexors, elbows, and ankles. The onset of Bethlem myopathy may be prenatal (characterized by decreased fetal movements), neonatal (hypotonia or torticollis), in early childhood (delayed motor milestones, muscle weakness, and contractures), or in adulthood (proximal weakness and Achilles tendon or long finger flexor contractures). Because of slow but ongoing progression, more than two-thirds of affected individuals over age 50 years rely on supportive means for outdoor mobility. Respiratory involvement is rare and seems to be related to more severe muscle weakness in later life. Ullrich CMD is characterized by congenital weakness and hypotonia, proximal joint contractures, and striking hyperlaxity of distal joints. Some affected children acquire the ability to walk independently; however, progression of the disease often results in later loss of ambulation. Early and severe respiratory involvement may require artificial ventilatory support in the first or second decade of life. Although originally described as separate entities, Bethlem myopathy and Ullrich CMD represent a clinical continuum in which individuals presenting with intermediate phenotypes could be considered to have either "mild Ullrich CMD" or "severe Bethlem myopathy." Diagnosis/testing. Diagnosis depends on typical clinical features, with the serum creatine kinase concentration usually being normal or only mildly elevated and muscle biopsy showing myopathic or dystrophic changes. In Bethlem myopathy, collagen VI immunolabeling of muscle is usually normal or shows subtle alterations only. In Ullrich CMD, collagen VI immunolabeling is absent or markedly reduced from the endomysium and basal lamina, but may be normal around capillaries. Mutations in the genes COL6A1, COL6A2, and COL6A3 are associated with Bethlem myopathy and Ullrich CMD. Molecular genetic testing is available on a clinical basis. Management. Bethlem myopathy/Ullrich CMD: Physiotherapy advice regarding stretching, splinting, and mobility aids; possible orthopedic assessment if surgery for Achilles tendon contractures is to be considered; respiratory surveillance for possible nocturnal hypoventilation. Prophylaxis of chest infections with vaccination and physiotherapy; aggressive treatment of pulmonary infections. In addition for Ullrich CMD: Assessment of nutritional status and growth; management of feeding difficulties. Active surveillance for development of scoliosis; therapy for scoliosis as indicated. Genetic counseling. Bethlem myopathy is inherited in an autosomal dominant manner and Ullrich CMD classically in an autosomal recessive manner although dominant inheritance secondary to de novo mutations can occur. Individuals with Bethlem myopathy are heterozygous for a COL6A1, COL6A2, or COL6A3 mutation and are symptomatic. They may have an affected parent. Parents of individuals with autosomal recessive Ullrich CMD are usually heterozygous for a COL6A1, COL6A2, or COL6A3 mutation, but do not appear to manifest related symptoms. Each child of an individual with Bethlem myopathy has a 50% chance of inheriting the condition; no individuals with Ullrich CMD have been known to reproduce. The risk to the sibs of the proband depends upon the genetic status of the proband's parents. For parents of a proband with proven autosomal recessive Ullrich CMD: at conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier. No laboratories offering direct molecular genetic testing for prenatal diagnosis for Bethlem myopathy or Ullrich CMD are listed in the GeneTests Laboratory Directory. However, prenatal testing may be available for families in which the disease-causing mutation has been identified in an affected family member.
Copyright © 1993-2011, University of Washington, Seattle. All rights reserved.
PMID: 20301676 http://www.ncbi.nlm.nih.gov/pubmed/20301676