Neuron-Specific Menin Deletion Leads to Synaptic Dysfunction and Cognitive Impairment by Modulating p35 Expression
Year: 2018
Type: article
Abstract: Menin (MEN1) is a critical modulator of tissue development and maintenance. As such, MEN1 mutations are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. Although menin is abundantly expressed in the nervous system, little is known with regard to its function in the adult brain. Here, we demonstrate that neuron-specific deletion of Men1 (CcKO) affects dendritic branching and spine formation, resulting in defects in synaptic function, learning, and memory. Furthermore, we find that menin binds to the p35 promoter region to facilitate p35 transcription. As a primary Cdk5 activator, p35 is expressed mainly in neurons and is critical for brain development and synaptic plasticity. Restoration of p35 expression in the hippocampus and cortex of Men1 CcKO mice rescues synaptic and cognitive deficits associated with Men1 deletion. These results reveal a critical role for menin in synaptic and cognitive function by modulating the p35-Cdk5 pathway.
Source: Cell Reports
Authors: Kai Zhuang, Changquan Huang, Lige Leng, Honghua Zheng, Yuehong Gao, Guimiao Chen, Zhilin Ji, Hao Sun, Yu Hu, Di Wu, Meng Shi, Huifang Li, Yingjun Zhao, Yunwu Zhang, Maoqiang Xue, Guojun Bu, Timothy Y. Huang, Huaxi Xu, Jie Zhang
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: University of Pennsylvania, Cure Alzheimer's Fund, National Natural Science Foundation of China, Natural Science Foundation of Fujian Province, National Institutes of Health, Program for New Century Excellent Talents in University, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, National Institute on Aging, National Institute of Neurological Disorders and Stroke
Awards: Molecular pathobiology of soluble TREM2 in Alzheimer's disease, Roles of SN27 in regulating glutamate receptors during neurodegeneration, G1851188853, G1981720942, The Role of Appoptosin in Alzheimer's Disease and Other Tauopathies, Cdk5 磷酸化Bag3 及其在神经元突触功能和凋亡中的作用与机制研究, Regulation of Protein Trafficking in Neurodegeneration, G3452454666, G358263164, The Role of DLG5 in Alzheimer's Disease, G4880680867, Menin通过IGFs信号通路调控胚胎神经系统发育的组蛋白甲基化修饰机制, G5027862427, Characterizing neuroprotective roles for SNX27 signaling pathways in AD and DS, G62269212, A role for TREM2/Abeta interactions in microglia-regulated AD pathogenesis, G6870282530, G7040251284, Identifying and characterizing gene(s) involved in beta-amyloid production., BAC Transgenic Mouse Models of TREM2 to Study Neuroprotective Mechanisms in AD, G8118044435, G8295456792, G9000377538, G9000379379
OpenAlex ID: W2883901424