title: A broken heart: a stretch too far: an overview of mouse models with mutations in stretch-sensor components.
abstract: With every heartbeat the heart must contract and relax. This seemingly trivial process critically needs tight control of contraction and relaxation phases, and extremely efficient coordination between these two phases to control blood flow and maintain cardiac homeostasis. To achieve this, specialized sensors are required to detect the inherent repeatedly changing environment and needs. One sensor is a stretch-sensor that monitors the filling of the ventricles. Its molecular identity and localization are only partly understood. Here we give a synopsis of the genetic models that leap into our understanding of stretch-sensors. We focus on the widely acknowledged sarcomeric sensor at the Z-disc and the costamere sensor at the sarcolemma. Recently, several novel components of both sensors were discovered. Given that these two sensors seem physically connected, it is likely that these two models are not mutually exclusive and might even communicate. We describe briefly how candidate and known proteins within these sensors receive and transduce mechanical signals in the cardiomyocyte that lead to changes in gene expression underlying homeostasis and its restoration in the heart. Emphasis is placed on the putative link between altered stretch-sensor function and heart failure observed in different genetic mouse models of stretch-sensor components.
authors: Laboratory of Molecular Biology (Celgen), Department of Molecular and Developmental Genetics (VIB11), Flanders Institute of Biotechnology (VIB), Leuven, Belgium.
authors: Luk
authors: L
authors: Cox
authors: Lieve
authors: L
authors: Umans
authors: Frederique
authors: F
authors: Cornelis
authors: Danny
authors: D
authors: Huylebroeck
authors: An
authors: A
authors: Zwijsen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008465:Mechanoreceptors / Q000502:physiology*; D051379:Mice; D009154:Mutation / Q000235:genetics*