CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome.

Bürgi J; Kunz B; Abrami L; Deuquet J; Piersigilli A; Scholl-Bürgi S; Lausch E; Unger S; Superti-Furga A; Bonaldo P; van der Goot FG

doi:10.1038/ncomms15861

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Journal article

CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome.

Bürgi J Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Kunz B Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Abrami L Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Deuquet J Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Piersigilli A Comparative Mouse Physiology Platform, Faculty of Life Sciences, EPFL, Lausanne 1015, Switzerland.
Scholl-Bürgi S Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Anichstrasse 35, 6020 Innsbruck, Austria.
Lausch E Department of Pediatrics, University of Freiburg, Freiburg 79106, Germany.
Unger S Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne 1011, Switzerland.
Superti-Furga A Division of Molecular Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne 1011, Switzerland.
Bonaldo P Department of Molecular Medicine, University of Padova, Padova 35122, Italy.
van der Goot FG Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.

2017-06-13

Published in:

Nature communications. - 2017

English Loss-of-function mutations in capillary morphogenesis gene 2 (CMG2/ANTXR2), a transmembrane surface protein, cause hyaline fibromatosis syndrome (HFS), a severe genetic disorder that is characterized by large subcutaneous nodules, gingival hypertrophy and severe painful joint contracture. Here we show that CMG2 is an important regulator of collagen VI homoeostasis. CMG2 loss of function promotes accumulation of collagen VI in patients, leading in particular to nodule formation. Similarly, collagen VI accumulates massively in uteri of Antxr2-/- mice, which do not display changes in collagen gene expression, and leads to progressive fibrosis and sterility. Crossing Antxr2-/- with Col6a1-/- mice leads to restoration of uterine structure and reversion of female infertility. We also demonstrate that CMG2 may act as a signalling receptor for collagen VI and mediates its intracellular degradation.

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