RT Journal Article
T1 Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43
A1 Maroto Martínez, Irene Berenice
A1 Costas Insúa, Carlos
A1 Montero Fernández, Carlos
A1 Martín Herranz, Ricardo
A1 García Font, Nuria
A1 Sánchez-Prieto Borja, José
A1 Galve Roperh, Ismael
A1 Rodríguez Crespo, José Ignacio
A1 Guzmán Pastor, Manuel
AB The type-1 cannabinoid receptor (CB1R) is widely expressed in excitatory and inhibitory nerve terminals, and by suppressing neurotransmitter release, its activation modulates neural circuits and brain function. While the interaction of CB1R with various intracellular proteins is thought to alter receptor signaling, the identity and role of these proteins are poorly understood. Using a high-throughput proteomic analysis complemented with an array of in vitro and in vivo approaches in the mouse brain, we report that the C-terminal, intracellular domain of CB1R interacts specifically with growth-associated protein of 43 kDa (GAP43). The CB1R-GAP43 interaction occurs selectively at mossy cell axon boutons, which establish excitatory synapses with dentate granule cells in the hippocampus. This interaction impairs CB1R-mediated suppression of mossy cell to granule cell transmission, thereby inhibiting cannabinoid-mediated anti-convulsant activity in mice. Thus, GAP43 acts as a synapse type-specific regulatory partner of CB1R that hampers CB1R-mediated effects on hippocampal circuit function.
PB Nature Communications
SN 2041-1723
YR 2023
FD 2023-04-21
LK https://hdl.handle.net/20.500.14352/131829
UL https://hdl.handle.net/20.500.14352/131829
LA eng
NO Maroto IB, Costas-Insua C, Berthoux C, Moreno E, Ruiz-Calvo A, Montero-Fernández C,  Macías-Camero A, Martín R, García-Font N, Sánchez-Prieto J, Marsicano G, Bellocchio L, Canela EI, Casadó V, Galve-Roperh I, Núñez Á, Fernández de Sevilla D, Rodríguez-Crespo I, Castillo PE, Guzmán M. Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43. Nat Commun. 2023 Apr 21;14(1):2303.
DS Docta Complutense
RD 26 feb 2026