RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy.
RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy.
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RAB39B 缺乏会部分通过损害自噬来损害学习和记忆
DOI：
10.3389/fcell.2020.598622
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发表时间：
2020
影响因子：
5.5
通讯作者：
Zhang YW
中科院分区：
文献类型：
--
作者：
Niu M;Zheng N;Wang Z;Gao Y;Luo X;Chen Z;Fu X;Wang Y;Wang T;Liu M;Yao T;Yao P;Meng J;Zhou Y;Ge Y;Wang Z;Ma Q;Xu H;Zhang YW
RAB39B位于X染色体上，编码RAB39B蛋白，属于RAB家族。RAB39B突变已知与x连锁智力残疾（XLID）、帕金森病和自闭症有关。然而，RAB39B的病理/生理功能在很大程度上仍然未知。在本研究中，我们建立了Rab39b基因敲除（KO）小鼠，其总体出生率和形态与野生型小鼠一样正常。然而，Rab39b缺乏导致2个月大的小鼠焦虑减少，学习和记忆受损。Rab39b缺失导致突触结构和功能受损，突触后密度（PSD）中NMDA受体减少。RAB39B缺乏也会在基础水平上降低自噬通量，这可能被雷帕霉素诱导的自噬激活所覆盖。此外，雷帕霉素治疗部分恢复了Rab39b KO小鼠受损的记忆和突触可塑性，而不影响NMDA受体的PSD分布。综上所述，RAB39B在调节自噬和突触形成中发挥重要作用，靶向自噬可能具有治疗RAB39B功能缺失突变引起的XLID的潜力。
RAB39B is located on the X chromosome and encodes the RAB39B protein that belongs to the RAB family. Mutations in RAB39B are known to be associated with X-linked intellectual disability (XLID), Parkinson’s disease, and autism. However, the patho/physiological functions of RAB39B remain largely unknown. In the present study, we established Rab39b knockout (KO) mice, which exhibited overall normal birth rate and morphologies as wild type mice. However, Rab39b deficiency led to reduced anxiety and impaired learning and memory in 2 months old mice. Deletion of Rab39b resulted in impairments of synaptic structures and functions, with reductions in NMDA receptors in the postsynaptic density (PSD). RAB39B deficiency also compromised autophagic flux at basal level, which could be overridden by rapamycin-induced autophagy activation. Further, treatment with rapamycin partially rescued impaired memory and synaptic plasticity in Rab39b KO mice, without affecting the PSD distribution of NMDA receptors. Together, these results suggest that RAB39B plays an important role in regulating both autophagy and synapse formation, and that targeting autophagy may have potential for treating XLID caused by RAB39B loss-of-function mutations.
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影响因子：
16.6
作者：
Mignogna ML;Giannandrea M;Gurgone A;Fanelli F;Raimondi F;Mapelli L;Bassani S;Fang H;Van Anken E;Alessio M;Passafaro M;Gatti S;Esteban JA;Huganir R;D'Adamo P
通讯作者：
D'Adamo P
DOI：
10.1212/nxg.0000000000000009
发表时间：
2015-06
期刊：
Neurology. Genetics
影响因子：
--
作者：
Lesage S;Bras J;Cormier-Dequaire F;Condroyer C;Nicolas A;Darwent L;Guerreiro R;Majounie E;Federoff M;Heutink P;Wood NW;Gasser T;Hardy J;Tison F;Singleton A;Brice A;French Parkinson's Disease Genetics Study Group (PDG) and the International Parkinson's Disease Genomics Consortium (IPDGC)
通讯作者：
French Parkinson's Disease Genetics Study Group (PDG) and the International Parkinson's Disease Genomics Consortium (IPDGC)
影响因子：
15.1
作者：
Mata IF;Jang Y;Kim CH;Hanna DS;Dorschner MO;Samii A;Agarwal P;Roberts JW;Klepitskaya O;Shprecher DR;Chung KA;Factor SA;Espay AJ;Revilla FJ;Higgins DS;Litvan I;Leverenz JB;Yearout D;Inca-Martinez M;Martinez E;Thompson TR;Cholerton BA;Hu SC;Edwards KL;Kim KS;Zabetian CP
通讯作者：
Zabetian CP
影响因子：
--
作者：
Corbier, Camille;Sellier, Chantal
通讯作者：
Sellier, Chantal
影响因子：
1.7
作者：
Cheng, H;Ma, Y;Mao, Y
通讯作者：
Mao, Y