Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex Regulating Collagen Lysyl Hydroxylation.

Autor:	Heard ME; Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Besio R; Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Weis M; Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, United States of America., Rai J; Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, United States of America., Hudson DM; Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, United States of America., Dimori M; Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Zimmerman SM; Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Kamykowski JA; Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Hogue WR; Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Swain FL; Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Burdine MS; Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Mackintosh SG; Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Tackett AJ; Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Suva LJ; Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America., Eyre DR; Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, United States of America., Morello R; Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.; Division of Genetics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Jazyk:	angličtina
Zdroj:	PLoS genetics [PLoS Genet] 2016 Apr 27; Vol. 12 (4), pp. e1006002. Date of Electronic Publication: 2016 Apr 27 (Print Publication: 2016).
DOI:	10.1371/journal.pgen.1006002
Abstrakt:	Collagen is a major component of the extracellular matrix and its integrity is essential for connective tissue and organ function. The importance of proteins involved in intracellular collagen post-translational modification, folding and transport was recently highlighted from studies on recessive forms of osteogenesis imperfecta (OI). Here we describe the critical role of SC65 (Synaptonemal Complex 65, P3H4), a leprecan-family member, as part of an endoplasmic reticulum (ER) complex with prolyl 3-hydroxylase 3. This complex affects the activity of lysyl-hydroxylase 1 potentially through interactions with the enzyme and/or cyclophilin B. Loss of Sc65 in the mouse results in instability of this complex, altered collagen lysine hydroxylation and cross-linking leading to connective tissue defects that include low bone mass and skin fragility. This is the first indication of a prolyl-hydroxylase complex in the ER controlling lysyl-hydroxylase activity during collagen synthesis.
Databáze:	MEDLINE
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