Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20363
Título
A mammalian-specific Alex3/Gαq protein complex regulates mitochondrial trafficking, dendritic complexity, and neuronal survival.
Autor(es)
Izquierdo-Villalba, Ismael | Mirra, Serena | Manso, Yasmina | Parcerisas, Antoni | Rubio, Javier | Del Valle, Jaume | Gil-Bea, Francisco J | Ulloa, Fausto | Herrero-Lorenzo, Marina | Verdaguer, Ester | Benincá, Cristiane | Castro-Torres, Rubén D | Rebollo, Elena | Marfany, Gemma | Auladell, Carme | Navarro, Xavier | Enriquez, Jose Antonio CNIC | López de Munain, Adolfo | Soriano, Eduardo | Aragay, Anna M
Fecha de publicación
2024-02-06
Cita
Sci Signal. 2024 Feb 6;17(822):eabq1007.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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 Gαq inhibited mitochondrial trafficking in neurons through a mechanism that was independent of the canonical downstream PLCβ pathway. Mitoproteome analysis revealed that Gαq interacted 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 Gαq on 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/Gαq mitochondrial complex, which enables control of mitochondrial trafficking and neuronal death by GPCRs.
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