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P-Rex1 Controls Sphingosine 1-Phosphate Receptor Signalling, Morphology, and Cell-Cycle Progression in Neuronal Cells
- Source :
- Cells, Volume 10, Issue 9, Cells, Vol 10, Iss 2474, p 2474 (2021)
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- rac1 GTP-Binding Protein
QH301-705.5
Sphingosine-1-phosphate receptor
G protein-coupled receptor (GPCR)
cell-cycle progression
Rac3
P-Rex1
Cell morphology
PC12 Cells
Article
Adenylyl cyclase
chemistry.chemical_compound
GPCR
Cell Movement
Sphingosine
Neurites
Animals
Guanine Nucleotide Exchange Factors
G protein-coupled receptor
Biology (General)
GEF
Sphingosine-1-Phosphate Receptors
S1PR1
Cell Proliferation
Neurons
cell morphology
Cell Cycle
Rho GTPase
General Medicine
neuronal signalling
Cell biology
Rats
rac GTP-Binding Proteins
Rac GTP-Binding Proteins
chemistry
guanine-nucleotide exchange factor
Signal transduction
Lysophospholipids
Rac1
Signal Transduction
Subjects
Details
- ISSN :
- 20734409
- Volume :
- 10
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cells
- Accession number :
- edsair.doi.dedup.....a7663a5942426f1cec1c9c27fde2f228