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  3. HAP1 interacts with 14-3-3 to regulate epileptic seizure via GABAAR-mediated inhibitory synaptic transmission in pentylenetetrazole rat model

HAP1 interacts with 14-3-3 to regulate epileptic seizure via GABAAR-mediated inhibitory synaptic transmission in pentylenetetrazole rat model

  • Neurosci Res. 2022 Sep:182:7-14. doi: 10.1016/j.neures.2022.05.006.
Yuetao Wen 1,  Guangliang Zhang 1,  Lin Liu 2,  Peng Zhang 3,  Lan Lin 4,  Rong Mei 4,  Fengli Zhang 4,  Yangmei Chen 3,  Rong Li 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, Chongqing, China.
  • 2 Department of Endoscopy center, Chongqing Jiangjin District Hospital of Traditional Chinese Medicine, Chongqing, China.
  • 3 Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Department of Neurology, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
  • 5 Department of Neurology, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. Electronic address: lirong0919@163.com.
PMID: 35609730 DOI: 10.1016/j.neures.2022.05.006
Abstract

Disruption of γ-aminobutyric acid type A receptors (GABAARs) synaptic clustering and a decrease number in the plasma membrane are thought to contribute to the alteration in the balance between excitatory and inhibitory neurotransmission in the epilepsy. Thus, it is important to elucidate the molecular mechanisms that regulate the stabilities of surface GABAARs populations as well as their concentrations at inhibitory synapses. However, the mechanism that delivers GABAARs to plasma membrane has not been conclusively determined. Our previous research indicated that huntingtin-associated protein 1 (HAP1), a major facilitator of pathological variations in membrane trafficking, modulates epileptic seizure by regulating GABAARs-mediated inhibitory synaptic transmission in pentylenetetrazole (PTZ)-induced epileptic rats. However, a detailed molecular interaction networks comprising GABAARs and HAP1 is necessary for studying and investigating new treatment targets for epilepsy. In this study, we indicate that HAP1 specifically interacts with 14-3-3, a protein that functions as a chaperone, forming a cargo adaptor complex to regulate surface GABAARs expression and the inhibitory post-synaptic current amplitudes. Disrupting the HAP1/14-3-3 complex decreases the strength of GABAARs-mediated inhibitory synaptic transmission in epilepsy. Taken together, HAP1/14-3-3 complex is linked to inhibitory synaptic transmission in evoking seizures, therefore, it is a possible drug target for epilepsy.

Keywords

14–3–3; Epileptic seizure; GABA(A)Rβ2/3; HAP1; Inhibitory synaptic.

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