Brain G-protein proteolysis by calpain: enhancement by lithium

Angela F. Greenwood, Richard S Jope

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 languageEnglish
Pages (from-to)320-326
Number of pages7
JournalBrain Research
Volume636
Issue number2
DOIs
StatePublished - Feb 14 1994
Externally publishedYes

Fingerprint

Calpain
Lithium
GTP-Binding Proteins
Proteolysis
Brain
Dissociative Disorders
Heterotrimeric GTP-Binding Proteins
Neuronal Plasticity
Membranes
Bipolar Disorder
Cerebral Cortex
Signal Transduction
Pharmaceutical Preparations

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 journalArticle

Greenwood, Angela F. ; Jope, Richard S. / Brain G-protein proteolysis by calpain : enhancement by lithium. In: Brain Research. 1994 ; Vol. 636, No. 2. pp. 320-326.
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