Glycosylphosphatidylinositol-Anchored Proteins as Regulators of Cortical Cytoskeleton.
Glycosylphosphatidylinositol-anchored proteins (GPI-AP) are important players in reception and signal transduction, cell adhesion, guidance, formation of immune synapses, and endocytosis. At that, a particular GPI-AP can have different activities depending on a ligand. It is known that GPI-AP oligomer creates a lipid raft in its base on plasma membrane, which serves as a signaling platform for binding and activation of src-family kinases. Yet, this does not explain different activities of GPI-APs. Meanwhile, it has been shown that short-lived actomyosin complexes are bound to GPI-APs through lipid rafts. Here, we hypothesize that cell cortical cytoskeleton is the main target of GPI-AP signaling. Our hypothesis is based on the fact that the GPI-AP-induced lipid raft bound to actin filaments and anionic lipids of this raft is known to interact with and activate various actin-nucleating factors, such as formins and N-WASP. It is also known that these and other actin-regulating proteins are activated by src-family kinases directly or through their effectors, such as cortactin and abl-kinases. Regulation of cytoskeleton by GPI-APs may have impact on morphogenesis, cell guidance, and endocytosis, as well as on signaling of other receptors. To evaluate our hypothesis, we have comprehensively considered physiological activities of two GPI-APs - urokinase receptor and T-cadherin.
Lomonosov Moscow State University, Faculty of Medicine, Moscow, 119992, Russia. sharonov@gmail.com.
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Sharonov
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Balatskaya
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Tkachuk
D021941:Caveolae / Q000378:metabolism; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D021962:Membrane Microdomains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism
C486562:CAPRIN1 protein, human; D018797:Cell Cycle Proteins; D008024:Ligands; D009218:Myosins