Abstract
The plasma membrane allows the cell to sense and adapt to changes in the extracellular environment by relaying external inputs via intracellular signaling networks. One central cellular signaling pathway is the Hippo pathway, which regulates homeostasis and plays chief roles in carcinogenesis and regenerative processes. Recent studies have found that mechanical stimuli and diffusible chemical components can regulate the Hippo pathway primarily through receptors embedded in the plasma membrane. Morphologically defined structures within the plasma membrane, such as cellular junctions, focal adhesions, primary cilia, caveolae, clathrin-coated pits, and plaques play additional key roles. Here, we discuss recent evidence highlighting the importance of these specialized plasma membrane domains in cellular feedback via the Hippo pathway.
Highlights
The plasma membrane is essential for cell integrity and serves as an interface to sense and respond to changes in the extracellular environment [1]
The Hippo Pathway and Regulation of YAP/TAZ on five (YAP)/TAZ The core Hippo pathway signaling cascade in mammals is comprised of a serine/threonine kinase cascade consisting of MST1/2, interacting with the scaffolding proteins Salvador homolog 1 (SAV1) and neurofibromatosis type 2 (NF2/Merlin), as well as LATS1/2, which interact with MOB kinase activator 1A and B (MOB1A and B) [10,16,154,155] (Figure I)
Hippo (MST1/2)-independent, LATS1/2-mediated regulation of YAP/TAZ occurs via the MAP4K kinase family [154], as well as by STK25 [156]
Summary
The plasma membrane allows the cell to sense and adapt to changes in the extracellular environment by relaying external inputs via intracellular signaling networks. One central cellular signaling pathway is the Hippo pathway, which regulates homeostasis and plays chief roles in carcinogenesis and regenerative processes. Recent studies have found that mechanical stimuli and diffusible chemical components can regulate the Hippo pathway primarily through receptors embedded in the plasma membrane. Defined structures within the plasma membrane, such as cellular junctions, focal adhesions, primary cilia, caveolae, clathrin-coated pits, and plaques play additional key roles. We discuss recent evidence highlighting the importance of these specialized plasma membrane domains in cellular feedback via the Hippo pathway
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