Editorial: Phosphoinositides and their phosphatases: Linking electrical and chemical signals in biological processes
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چکیده
Citation: Kohout SC and Villalba-Galea CA (2015) Editorial: Phosphoinositides and their phosphatases: Linking electrical and chemical signals in biological processes. The voltage-sensing phosphatase (VSP) has changed the way we think about both cellular electrical activity and PIPs (phosphatidylinositol phosphates). Originally discovered in 1999 (Chen et al., 1999), these proteins were not recognized as electrically-controlled enzymes until 2005 (Murata et al., 2005). They constitute the first, and so far the only, example of an enzyme linking electrical signals at the plasma membrane to the catalysis of PIPs (Murata et al., 2005), a ubiquitous family of intracellular signaling molecules (Di Paolo and De Camilli, 2006; Balla, 2013). Before the discovery of VSP, there were no known direct links between the two. Textbook examples would represent this connection with arrows, alluding to indirect or " yet-to-be-defined " signaling pathways. Now we know that VSP serves as a direct connection between the electrical nature of the cell and PIPs, lipid second messengers that are critical for cell survival. However, many questions remain unanswered regarding VSP and its electrical regulation of cellular processes. With the discovery of VSP, the membrane potential must now be considered when studying PIP regulators. PIPs are involved in almost all aspects of cell physiology from survival, proliferation, and migration to pre-programed cell death These gradients in the concentration of PIPs are necessary for activation of Rac and Rho leading to cell motion. PIPs are also crucial for cell growth: PI(3,4,5)P 3 activates the mTor cascade leading to increased protein, membrane, and nucleic acid production (Dibble and Manning, 2013). Many human diseases have been associated with altered homeostasis of PIPs, including cancer, developmental disorders, and Alzheimer's disease Though the physiological relevance of VSP is not yet defined, it is still crucial to human health to understand how PIPs are regulated and that now includes VSP. All cells have an asymmetric composition of ions across their plasma membrane, which, combined with selective permeabilities for these ions, results in a difference in the electrical potential across their plasma membrane. This difference, called the membrane potential, constitutes a form of cell signaling and a source of energy, both driving many biological processes. This electrical potential difference powers neuronal excitability as well as more general processes like Regulation by the membrane potential has long been the sole purview of ion channels and transporters and that has influenced what questions are asked regarding the changing potential. …
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