Abstract
In highly organized multicellular organisms such as humans, the functions of an individual cell are dependent on signal transduction through G protein-coupled receptors (GPCRs) and subsequently heterotrimeric G proteins. As most of the elements belonging to the signal transduction system are bound to lipid membranes, researchers are showing increasing interest in studying the accompanying protein–lipid interactions, which have been demonstrated to not only provide the environment but also regulate proper and efficient signal transduction. The mode of interaction between the cell membrane and G proteins is well known. Despite this, the recognition mechanisms at the molecular level and how the individual G protein-membrane attachment signals are interrelated in the process of the complex control of membrane targeting of G proteins remain unelucidated. This review focuses on the mechanisms by which mammalian Gα subunits of G proteins interact with lipids and the factors responsible for the specificity of membrane association. We summarize recent data on how these signaling proteins are precisely targeted to a specific site in the membrane region by introducing well-defined modifications as well as through the presence of polybasic regions within these proteins and interactions with other components of the heterocomplex.
Highlights
The correct development of cells depends on how they respond to various environmental factors and how they develop stress tolerance
Some G protein-coupled receptors (GPCRs) can retain or recover the ability to activate G proteins after internalization and subsequently activate G proteins associated with the cell membrane, and those located in the cytoplasm, within endosomes or membrane compartments in the biosynthetic pathway
While at least one palmitoyl lipid anchor is present on all Gα subunits, except for Gαt and Gαg, the presence of the myristoyl group differs across all Gα families and even among one family
Summary
The correct development of cells depends on how they respond to various environmental factors and how they develop stress tolerance. Some GPCRs can retain or recover the ability to activate G proteins after internalization and subsequently activate G proteins associated with the cell membrane, and those located in the cytoplasm, within endosomes or membrane compartments in the biosynthetic pathway (review: [20,21]) This fact makes signaling through G proteins even more complicated due to differences in protein-partner availability and differences in the environment in which transduction elements are located. This review aims to provide an overview of the mechanisms of Gα subunits’ interaction with lipids and factors responsible for the specificity of membrane association This knowledge is very important as it shows how different signaling proteins can be precisely targeted at a predestined location by incorporating well-defined modifications. Gα itself acts as a crucial modulator of the membrane localization of the full complex [31]
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