title: What do mechanotransduction, Hippo, Wnt, and TGFβ have in common? YAP and TAZ as key orchestrating molecules in ocular health and disease.
abstract: Cells in vivo are exposed to a complex signaling environment. Biochemical signaling modalities, such as secreted proteins, specific extracellular matrix domains and ion fluxes certainly compose an important set of regulatory signals to cells. However, these signals are not exerted in isolation, but rather in concert with biophysical cues of the surrounding tissue, such as stiffness and topography. In this review, we attempt to highlight the biophysical attributes of ocular tissues and their influence on cellular behavior. Additionally, we introduce the proteins YAP and TAZ as targets of biophysical and biochemical signaling and important agonists and antagonists of numerous signaling pathways, including TGFβ and Wnt. We frame the discussion around this extensive signaling crosstalk, which allows YAP and TAZ to act as orchestrating molecules, capable of integrating biophysical and biochemical cues into a broad cellular response. Finally, while we draw on research from various fields to provide a full picture of YAP and TAZ, we attempt to highlight the intersections with vision science and the exciting work that has already been performed.
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, 1 Shields Ave., Davis, CA 95616, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Morgan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murphy
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
mesh_terms: D000217:Acyltransferases; D018797:Cell Cycle Proteins; D005123:Eye / Q000378:metabolism*; D005128:Eye Diseases / Q000378:metabolism*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; C456659:YY1AP1 protein, human; D000217:Acyltransferases; C108675:TAFAZZIN protein, human; D017346:Protein Serine-Threonine Kinases
keywords: TAZ; TGFβ; Wnt; YAP; biophysical cueing; hippo; mechanotransduction