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

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

  • PLoS Genet. 2016 Apr 27;12(4):e1006002. doi: 10.1371/journal.pgen.1006002.
Melissa E Heard 1,  Roberta Besio 1,  MaryAnn Weis 2,  Jyoti Rai 2,  David M Hudson 2,  Milena Dimori 1,  Sarah M Zimmerman 1,  Jeffrey A Kamykowski 1,  William R Hogue 3,  Frances L Swain 3,  Marie S Burdine 4,  Samuel G Mackintosh 4,  Alan J Tackett 4,  Larry J Suva 3,  David R Eyre 2,  Roy Morello 1 5
Affiliations

Affiliations

  • 1 Department of Physiology & Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
  • 2 Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, Washington, United States of America.
  • 3 Department of Orthopaedic Surgery, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
  • 4 Department of Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
  • 5 Division of Genetics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
PMID: 27119146 DOI: 10.1371/journal.pgen.1006002
Abstract

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.

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