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  • Leptin increases GABAergic synaptogenesis through the Rho guanine exchange factor β-PIX in developing hippocampal neurons.

Leptin increases GABAergic synaptogenesis through the Rho guanine exchange factor β-PIX in developing hippocampal neurons.

Science signaling (2021-05-20)
Gulcan Semra Sahin, Jose Luis Rodriguez-Llamas, Crystal Dillon, Igor Medina, Suzanne M Appleyard, Jean-Luc Gaiarsa, Gary A Wayman
摘要

Developing hippocampal neurons undergo rapid synaptogenesis in response to neurotrophic signals to form and refine circuit connections. The adipokine leptin is a satiety factor with neurotrophic actions, which potentiates both glutamatergic and GABAergic synaptogenesis in the hippocampus during neonatal development. Brief exposure to leptin enhances GABAA receptor-dependent synaptic currents in hippocampal neurons. Here, using molecular and electrophysiological techniques, we found that leptin increased the surface localization of GABAA receptors and the number of functional GABAergic synapses in hippocampal cultures from male and female rat pups. Leptin increased the interaction between GABAA receptors and the Rho guanine exchange factor β-PIX (a scaffolding protein at GABAergic postsynaptic sites) in a manner dependent on the kinase CaMKK. We also found that the leptin receptor and β-PIX formed a complex, the amount of which transiently increased upon leptin receptor activation. Furthermore, Tyr985 in the leptin receptor and the SH3 domain of β-PIX are crucial for this interaction, which was required for the developmental increase in GABAergic synaptogenesis. Our results suggest a mechanism by which leptin promotes GABAergic synaptogenesis in hippocampal neurons and reveal further complexity in leptin receptor signaling and its interactome.

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Sigma-Aldrich
脱氧核糖核酸酶 I 来源于牛胰腺, Type IV, lyophilized powder, ≥2,000 Kunitz units/mg protein
Sigma-Aldrich
木瓜蛋白酶 来源于木瓜乳液, buffered aqueous suspension, 2× Crystallized, ≥16 units/mg protein
Sigma-Aldrich
抗GABA A受体β2,3链抗体,克隆BD17, clone BD17, Chemicon®, from mouse
Sigma-Aldrich
Anti-Beta Pix, SH3 Domain Antibody, from rabbit, purified by affinity chromatography