Regulation of post-Golgi LH3 trafficking is essential for collagen homeostasis
journal contributionposted on 17.05.2017, 14:06 by Blerida Banushi, Federico Forneris, Anna Straatman-Iwanowska, Adam Strange, Anne-Marie Lyne, Clare Rogerson, Jemima J. Burden, Wendy E. Heywood, Joanna Hanley, Ivan Doykov, Kornelis R. Straatman, Holly Smith, Danai Bem, Janos Kriston-Vizi, Gema Ariceta, Maija Risteli, Chunguang Wang, Rosalyn E. Ardill, Marcin Zaniew, Julita Latka-Grot, Simon N. Waddington, S. J. Howe, Francesco Ferraro, Asllan Gjinovci, Scott Lawrence, Mark Marsh, Mark Girolami, Laurent Bozec, Kevin Mills, Paul Gissen
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.