Reggie-1 and reggie-2 (flotillins) participate in Rab11a-dependent cargo trafficking, spine synapse formation and LTP-related AMPA receptor (GluA1) surface exposure in mouse hippocampal neurons
Reggie-1 and reggie-2 (flotillins) participate in Rab11a-dependent cargo trafficking, spine synapse formation and LTP-related AMPA receptor (GluA1) surface exposure in mouse hippocampal neurons
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DOI：
10.1016/j.expneurol.2016.12.007
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发表时间：
2017-03-01
影响因子：
5.3
通讯作者：
Stuermer, Claudia A. O.
中科院分区：
文献类型：
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作者：
Bodrikov, Vsevolod;Pauschert, Aline;Stuermer, Claudia A. O.
Reggie-1和Reggie-2（漂浮蛋白）位于再循环囊泡中，并与Rabla共同促进货物的靶向递送。再循环对于突触的形成是必不可少的，这表明reggies和Rabla可能调节棘突触的发育。再循环囊泡为树突状细胞生长提供货物，并为长时程增强（LTP）诱导的表面暴露再循环表面谷氨酸受体（AMPAR，GluA）。在这里，我们发现减少了脊髓突触和损伤的体外相关的LTP海马神经元从雷吉-1 k.o.（Flot 2-/-）小鼠在培养物中成熟。这些缺陷显然是由于10 div reggie-1 k.o.的实时成像显示PSD-95的运输减少所致。（Flot 2-/-）神经元，并可能损害去往棘的货物的共转运：N-钙粘蛋白和谷氨酸受体GluA 1和GluN 1。货物运输受损和突触减少也出现在reggie-1 siRNA、reggie-2 siRNA以及reggie-1和-2 siRNA处理的神经元中，并且在siRNA和k.o.通过reggie-1-EGFP和CA-Rab 11 a-EGFP拯救神经元。而reggie-1 k.o.突触特异性蛋白质的表达也发生了相应的变化。（Flot 2-/-）脑中，这在体外成熟的神经元中没有发生。我们的工作表明，reggie-1和reggie-2在Rabl 1a回收容器中参与P513-95、N-cadherin、GluA 1和GluN 1的转运，并与重要的信号分子一起促进脊髓定向运输、脊髓突触形成和LTP的体外相关性。(C)2016 Elsevier Inc. All rights reserved.
Reggie-1 and -2 (flotillins) reside at recycling vesicles and promote jointly with Rabl la the targeted delivery of cargo. Recycling is essential for synapse formation suggesting that reggies and Rabl la may regulate the development of spine synapses. Recycling vesicles provide cargo for dendritic growth and recycle surface glutamate receptors (AMPAR, GluA) for long-term potentiation (LTP) induced surface exposure. Here, we show reduced number of spine synapses and impairment of an in vitro correlate of LTP in hippocampal neurons from reggie-1 k.o. (Flot2-/-) mice maturating in culture. These defects apparently result from reduced trafficking of PSD-95 revealed by live imaging of 10 div reggie-1 k.o. (Flot2-/-) neurons and likely impairs co-transport of cargo destined for spines: N-cadherin and the glutamate receptors GluA1 and GluN1. Impaired cargo trafficking and fewer synapses also emerged in reggie-1 siRNA, reggie-2 siRNA, and reggie-1 and -2 siRNA-treated neurons and was in siRNA and k.o. neurons rescued by reggie-1-EGFP and CA-Rab11 a-EGFP. While correlative expressional changes of specific synapse proteins were observed in reggie-1 k.o. (Flot2-/-) brains in vivo, this did not occur in neurons maturating in vitro. Our work suggests that reggie-1 and reggie-2 function at Rabl l a recycling containers in the transport of P513-95, N-cadherin, GluA1 and GluN1, and promote (together with significant signaling molecules) spine-directed trafficking, spine synapse formation and the in vitro correlate of LTP. (C) 2016 Elsevier Inc. All rights reserved.