Cardiac integrity and function depends on the ADAMTSL protein Lonely heart. Maik Drechsler, Ariane Schmidt, Heiko Meyer, Achim Paululat. Department of Zoology/Developmental Biology, University of Osnabrueck, Osnabrueck, Germany.

   Changes in ECM composition, turnover or homeostasis are crucial mediators of human cardiovascular disease leading to life threatening conditions. The formation and maintenance of a tissue specific ECM is therefore a vital task to maintain organ functionality. Using Drosophila as model of cardiac integrity we identified the ADAMTSL protein Loh as essential for the assembly and proper organization of a cardiac matrix composed of the collagen Prc. We found that mutations in loh lead to the disability of Prc to integrate correctly into the cardiac ECM during embryogenesis. Consequently, the adhesion of pericardial cells and alary muscles towards the heart tube get disrupted during post-embryonic stages, causing a loss of cardiac integrity and function. This results in the abolishment of hemolymph flow and a dramatic reduction of the fly's life span. On the mechanistic level we provide further evidence that Loh is able to recruit Prc to target tissues in vivo and therefore acts as a secreted receptor of this collagen. Our data, in combination with previous findings in mammals, demonstrate that the function of ADAMTS-like proteins in facilitating matrix formation and stability is evolutionary conserved and constitutes an important task to allow cardiac homeostasis.