Caveolae allow smooth muscles cells to adapt to stress through the Gαq/PLCβ pathway

Qifti, Androniqi

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Caveolae allow smooth muscles cells to adapt to stress through the Gαq/PLCβ pathway

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Phospholipase Cβ1 (PLCβ1) is a multifunctional protein localized mainly on the plasma membrane that also binds to stress granule (SG) proteins in the cytoplasm. While activation of Gαq, the membrane bound subunit of the GPCR, leads to the activation of PLCβ1 on the membrane, Gαq also binds to Caveolin-1 (Cav-1) at a different binding site. Cav-1, a fundamental component of the formation and maintenance of caveolae domains, stabilizes the activated state of Gαq enhancing the activation of PLCβ1 and prolonging the intracellular calcium efflux. Caveolae disruption and irregular stress granule assembly and disassembly have been implicated in several diseases including spontaneous hypertrophy (muscle enlargement of cardiac cells), ALS and autism spectrum disorder. Here we provide valuable insight into the ways cells adapt to different environmental stresses including hypo-osmotic stress, heat shock, cold shock, carbachol and arsenite treatment. This dissertation examines the effects of various environmental stresses in smooth muscle cells and their ability to adapt to them through the Gαq/PLCβ1 signaling. We found that all environmental stresses increase the number and size of PABPC1 and Ago2 related particles suggesting the increased incorporation of stress granules. We also found that loss of PLCβ1 from the cytoplasm promotes stress granule oligomerization. We next identified the caveolae involvement in this process and we were mainly interested in the role of Cav-1 and cavin-1. We discovered that caveolae deformation through mechanical stretch or Gαq activation promotes cavin-1 relocalization from the plasma membrane to the nucleus to impact transcription and translation. With that in mind, we wanted to understand the series of events taking place in the nucleus and identify genes whose production is severely affected due to the caveolae deformation. Overall, we found several anti-viral genes being upregulated when caveolae were deformed, leading to a novel discovery.

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