P-Rex1 Controls Sphingosine 1-Phosphate Receptor Signalling, Morphology, and Cell-Cycle Progression in Neuronal Cells.
Hubbard, Roderick E
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Hampson, E., Tsonou, E., Baker, M. J., Hornigold, D. C., Hubbard, R. E., Massey, A., & Welch, H. C. E. (2021). P-Rex1 Controls Sphingosine 1-Phosphate Receptor Signalling, Morphology, and Cell-Cycle Progression in Neuronal Cells.. Cells, 10 (9. ARTN 2474), 2474-2474. https://doi.org/10.3390/cells10092474
P-Rex1 is a guanine-nucleotide exchange factor (GEF) that activates Rac-type small G proteins in response to the stimulation of a range of receptors, particularly G protein-coupled receptors (GPCRs), to control cytoskeletal dynamics and other Rac-dependent cell responses. P-Rex1 is mainly expressed in leukocytes and neurons. Whereas its roles in leukocytes have been studied extensively, relatively little is known about its functions in neurons. Here, we used CRISPR/Cas9-mediated P-Rex1 deficiency in neuronal PC12 cells that stably overexpress the GPCR S1PR1, a receptor for sphingosine 1-phosphate (S1P), to investigate the role of P-Rex1 in neuronal GPCR signalling and cell responses. We show that P-Rex1 is required for the S1P-stimulated activation of Rac1 and Akt, basal Rac3 activity, and constitutive cAMP production in PC12-S1PR1 cells. The constitutive cAMP production was not due to increased expression levels of major neuronal adenylyl cyclases, suggesting that P-Rex1 may regulate adenylyl cyclase activity. P-Rex1 was required for maintenance of neurite protrusions and spreading in S1P-stimulated PC12-S1PR1 cells, as well as for cell-cycle progression and proliferation. In summary, we identified novel functional roles of P-Rex1 in neuronal Rac, Akt and cAMP signalling, as well as in neuronal cell-cycle progression and proliferation.
G protein-coupled receptor (GPCR), GEF, P-Rex1, Rac1, Rac3, Rho GTPase, cell morphology, cell proliferation, cell-cycle progression, guanine-nucleotide exchange factor, neuronal signalling, Animals, Cell Cycle, Cell Movement, Cell Proliferation, Guanine Nucleotide Exchange Factors, Lysophospholipids, Neurites, Neurons, PC12 Cells, Rats, Signal Transduction, Sphingosine, Sphingosine-1-Phosphate Receptors, rac GTP-Binding Proteins, rac1 GTP-Binding Protein
External DOI: https://doi.org/10.3390/cells10092474
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331221
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/