Abstract
Heterotrimeric G-proteins mediate many receptor-coupled signal transduction processes and the cellular concentrations of G-proteins are modulated by several factors, including development, activity, and drugs. The mechanisms causing changes in G-protein concentrations are mostly unknown. The purpose of this study was to determine if G-proteins could be proteolyzed by calpain, a calcium-activated neutral protease that has been linked with neuronal plasticity. In membranes prepared from rat cerebral cortex, calpain rapidly cleaved the α-subunit of Go but did not hydrolyze ß-subunits. Comparisons of the proteolysis of different α-subunits revealed that they were differentially susceptible to calpain-induced proteolysis in the order of αs > αo > αq > αi. Preincubation of cortical membranes with GTPγS, which binds to Gα and causes its dissociation from the ßγ dimer, reduced calpain-mediated proteolysis of αo. Lithium, the primary treatment for mania, enhanced the calpain-mediated proteolysis of αo in the heterotrimeric state but did not affect proteolysis of dissociated, GTPγS-bound αo. These results demonstrate that proteolysis by calpain is a potential mechanism by which cellular G-protein concentrations can be regulated.
| Original language | English |
|---|---|
| Pages (from-to) | 320-326 |
| Number of pages | 7 |
| Journal | Brain Research |
| Volume | 636 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 14 1994 |
| Externally published | Yes |
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Keywords
- Calpain
- G-protein
- Lithium
- Signal transduction
ASJC Scopus subject areas
- Developmental Biology
- Molecular Biology
- Clinical Neurology
- Neuroscience(all)
Cite this
Brain G-protein proteolysis by calpain : enhancement by lithium. / Greenwood, Angela F.; Jope, Richard S.
In: Brain Research, Vol. 636, No. 2, 14.02.1994, p. 320-326.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Brain G-protein proteolysis by calpain
T2 - enhancement by lithium
AU - Greenwood, Angela F.
AU - Jope, Richard S
PY - 1994/2/14
Y1 - 1994/2/14
N2 - Heterotrimeric G-proteins mediate many receptor-coupled signal transduction processes and the cellular concentrations of G-proteins are modulated by several factors, including development, activity, and drugs. The mechanisms causing changes in G-protein concentrations are mostly unknown. The purpose of this study was to determine if G-proteins could be proteolyzed by calpain, a calcium-activated neutral protease that has been linked with neuronal plasticity. In membranes prepared from rat cerebral cortex, calpain rapidly cleaved the α-subunit of Go but did not hydrolyze ß-subunits. Comparisons of the proteolysis of different α-subunits revealed that they were differentially susceptible to calpain-induced proteolysis in the order of αs > αo > αq > αi. Preincubation of cortical membranes with GTPγS, which binds to Gα and causes its dissociation from the ßγ dimer, reduced calpain-mediated proteolysis of αo. Lithium, the primary treatment for mania, enhanced the calpain-mediated proteolysis of αo in the heterotrimeric state but did not affect proteolysis of dissociated, GTPγS-bound αo. These results demonstrate that proteolysis by calpain is a potential mechanism by which cellular G-protein concentrations can be regulated.
AB - Heterotrimeric G-proteins mediate many receptor-coupled signal transduction processes and the cellular concentrations of G-proteins are modulated by several factors, including development, activity, and drugs. The mechanisms causing changes in G-protein concentrations are mostly unknown. The purpose of this study was to determine if G-proteins could be proteolyzed by calpain, a calcium-activated neutral protease that has been linked with neuronal plasticity. In membranes prepared from rat cerebral cortex, calpain rapidly cleaved the α-subunit of Go but did not hydrolyze ß-subunits. Comparisons of the proteolysis of different α-subunits revealed that they were differentially susceptible to calpain-induced proteolysis in the order of αs > αo > αq > αi. Preincubation of cortical membranes with GTPγS, which binds to Gα and causes its dissociation from the ßγ dimer, reduced calpain-mediated proteolysis of αo. Lithium, the primary treatment for mania, enhanced the calpain-mediated proteolysis of αo in the heterotrimeric state but did not affect proteolysis of dissociated, GTPγS-bound αo. These results demonstrate that proteolysis by calpain is a potential mechanism by which cellular G-protein concentrations can be regulated.
KW - Calpain
KW - G-protein
KW - Lithium
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=0028040099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028040099&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(94)91031-6
DO - 10.1016/0006-8993(94)91031-6
M3 - Article
C2 - 8012815
AN - SCOPUS:0028040099
VL - 636
SP - 320
EP - 326
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -