Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis
| Autor: | Banushi, Blerida, Forneris, Federico, Straatman-Iwanowska, Anna, Strange, Adam, Lyne, Anne-Marie, Rogerson, Clare, Burden, Jemima J., Heywood, Wendy E., Hanley, Joanna, Doykov, Ivan, Straatman, Kornelis R., Smith, Holly, Bem, Danai, Kriston-Vizi, Janos, Ariceta Iraola, Gema, Risteli, Maija, Wang, Chunguang, Ardill, Rosalyn E., Zaniew, Marcin, Latka-Grot, Julita, Waddington, Simon N., Howe, S. J., Ferraro, Francesco, Gjinovci, Asllan, Lawrence, Scott, Marsh, Mark, Girolami, Mark, Bozec, Laurent, Mills, Kevin, Gissen, Paul, Universitat Autònoma de Barcelona |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| Popis: | Post-translational modifications are necessary for collagen precursor molecules (procollagens) to acquire final shape and function. However, the mechanism and contribution of collagen modifications that occur outside the endoplasmic reticulum and Golgi are not understood. We discovered that VIPAR, with its partner proteins, regulate sorting of lysyl hydroxylase 3 (LH3, also known as PLOD3) into newly identified post-Golgi collagen IV carriers and that VIPAR-dependent sorting is essential for modification of lysines in multiple collagen types. Identification of structural and functional collagen abnormalities in cells and tissues from patients and murine models of the autosomal recessive multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis syndrome caused by VIPAR and VPS33B deficiencies confirmed our findings. Thus, regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis and for the development and function of multiple organs and tissues. Lysine hydroxylation of procollagen precursors by LH3 is required for collagen fibril crosslinking and stabilization. Here the authors show that the trafficking protein VIPAR is required for correct sorting of LH3 into post-Golgi collagen carriers and for correct collagen modification and structure |
| Databáze: | OpenAIRE |
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