Functional specialization of different PI3K isoforms for the control of neuronal architecture, synaptic plasticity, and cognition
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Título: | Functional specialization of different PI3K isoforms for the control of neuronal architecture, synaptic plasticity, and cognition |
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Autor/es: | Sánchez-Castillo, Carla | Cuartero, María I. | Fernández-Rodrigo, Alba | Briz, Víctor | López-García, Sergio | Jiménez-Sánchez, Raquel | López, Juan A. | Graupera, Mariona | Esteban, José A. |
Grupo/s de investigación o GITE: | Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS) |
Centro, Departamento o Servicio: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Palabras clave: | Neuronal architecture | Synaptic plasticity | Cognitive performance | PI3K isoforms | Functional specialization |
Fecha de publicación: | 23-nov-2022 |
Editor: | American Association for the Advancement of Science |
Cita bibliográfica: | Science Advances. 2022, 8: eabq8109. https://doi.org/10.1126/sciadv.abq8109 |
Resumen: | Neuronal connectivity and activity-dependent synaptic plasticity are fundamental properties that support brain function and cognitive performance. Phosphatidylinositol 3-kinase (PI3K) intracellular signaling controls multiple mechanisms mediating neuronal growth, synaptic structure, and plasticity. However, it is still unclear how these pleiotropic functions are integrated at molecular and cellular levels. To address this issue, we used neuron-specific virally delivered Cre expression to delete either p110α or p110β (the two major catalytic isoforms of type I PI3K) from the hippocampus of adult mice. We found that dendritic and postsynaptic structures are almost exclusively supported by p110α activity, whereas p110β controls neurotransmitter release and metabotropic glutamate receptor–dependent long-term depression at the presynaptic terminal. In addition to these separate functions, p110α and p110β jointly contribute to N-methyl-d-aspartate receptor–dependent postsynaptic long-term potentiation. This molecular and functional specialization is reflected in different proteomes controlled by each isoform and in distinct behavioral alterations for learning/memory and sociability in mice lacking p110α or p110β. |
Patrocinador/es: | This work was supported by the Spanish Ministry of Science and Innovation grants SAF2017-86983-R and PID2020-117651RB (to J.A.E.), Spanish Ministry of Science and Innovation grants SAF2017-89116R-P (FEDER/EU) and PID2020-116184RB (to M.G.), Carlos III Institute of Health-Fondo de Investigación Sanitaria grant PRB3 (IPT17/0019–ISCIII-SGEFI/ERDF, ProteoRed) and CIBERCV (to J.A.L.), Spanish Ministry of Economy postdoctoral contract IJCI-2015-25507 (to M.I.C.), Marie Curie cofund UAM-UE (EU project 713366) Intertalentum Postdoctoral Program (to V.B.), and Spanish Ministry of Science and Innovation predoctoral contracts (to C.S.-C., A.F.-R., and S.L.-G.). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). |
URI: | http://hdl.handle.net/10045/129894 |
ISSN: | 2375-2548 |
DOI: | 10.1126/sciadv.abq8109 |
Idioma: | eng |
Tipo: | info:eu-repo/semantics/article |
Derechos: | © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). |
Revisión científica: | si |
Versión del editor: | https://doi.org/10.1126/sciadv.abq8109 |
Aparece en las colecciones: | INV - NEUROVIS - Artículos de Revistas |
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