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A mammalian-specific Alex3/Gαqprotein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival
- Source :
- Science Signaling; February 2024, Vol. 17 Issue: 822
- Publication Year :
- 2024
-
Abstract
- Mitochondrial dynamics and trafficking are essential to provide the energy required for neurotransmission and neural activity. We investigated how G protein–coupled receptors (GPCRs) and G proteins control mitochondrial dynamics and trafficking. The activation of Gαqinhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCβ pathway. Mitoproteome analysis revealed that Gαqinteracted with the Eutherian-specific mitochondrial protein armadillo repeat–containing X-linked protein 3 (Alex3) and the Miro1/Trak2 complex, which acts as an adaptor for motor proteins involved in mitochondrial trafficking along dendrites and axons. By generating a CNS-specific Alex3 knockout mouse line, we demonstrated that Alex3 was required for the effects of Gαqon mitochondrial trafficking and dendritic growth in neurons. Alex3-deficient mice had altered amounts of ER stress response proteins, increased neuronal death, motor neuron loss, and severe motor deficits. These data revealed a mammalian-specific Alex3/Gαqmitochondrial complex, which enables control of mitochondrial trafficking and neuronal death by GPCRs.
Details
- Language :
- English
- ISSN :
- 19450877 and 19379145
- Volume :
- 17
- Issue :
- 822
- Database :
- Supplemental Index
- Journal :
- Science Signaling
- Publication Type :
- Periodical
- Accession number :
- ejs65398935
- Full Text :
- https://doi.org/10.1126/scisignal.abq1007