High basal expression and injury-induced down regulation of two regulator of G-protein signaling transcripts, RGS3 and RGS4 in primary sensory neurons.
The regulators of G-protein signaling (RGS) proteins are a family of intracellular modulators of G-protein coupled receptor (GPCR) sensitivity. They act as GTPase accelerating proteins returning the Galpha subunit back to an inactive latent state. We find that RGS3 and RGS4 are constitutively expressed at high levels in C-fiber primary sensory neurons in the adult rat dorsal root ganglion (DRG) and transection of the sciatic nerve results in a substantial down regulation of these transcripts. RGS4 mRNA is expressed only in GDNF-responsive neurons and GDNF supports the expression of this transcript in primary DRG cultures. A PDZ domain containing subtype of RGS3 is the most abundant and regulated form of this protein within the DRG. Decreased levels of RGS3 and RGS4 in injured sensory neurons is likely to result in an increased GPCR sensitivity, and therefore contribute to alterations in cellular function seen after such lesions.
Costigan
Michael
M
Neural Plasticity Research Group, Department of Anesthesia & Critical Care, Massachusetts General Hospital & Harvard Medical School, 13th Street, Building 149 (#4309), Charlestown, MA 02129, USA. Costigan@helix.mgh.harvard.edu
Samad
Tarek A
TA
Allchorne
Andrew
A
Lanoue
Christopher
C
Tate
Simon
S
Woolf
Clifford J
CJ
D000818:Animals; D019771:Axotomy; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D019204:GTP-Binding Proteins; D020690:GTPase-Activating Proteins; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000378:metabolism / Q000503:physiopathology; D017434:Protein Structure, Tertiary / Q000502:physiology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012097:Repressor Proteins; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000503:physiopathology
D020690:GTPase-Activating Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020710:RGS Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; C415085:Rgs3 protein, mouse; C437714:Rgs3 protein, rat; C098799:RGS4 protein; D019204:GTP-Binding Proteins