Soluble ICAM-5, a product of activity dependent proteolysis, increases mEPSC frequency and dendritic expression of GluA1.
Soluble ICAM-5, a product of activity dependent proteolysis, increases mEPSC frequency and dendritic expression of GluA1.
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DOI：
10.1371/journal.pone.0069136
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Conant K
中科院分区：
文献类型：
--
作者：
Lonskaya I;Partridge J;Lalchandani RR;Chung A;Lee T;Vicini S;Hoe HS;Lim ST;Conant K
基质金属蛋白酶（MMP）是锌依赖性内肽酶，其可以以活性依赖的方式从神经元释放，以在各种形式的学习和记忆中发挥作用。MMP抑制剂损害海马长时程增强（LTP）、空间记忆和药物成瘾的行为相关性。由于MMPs被认为通过β1整联蛋白依赖性机制影响LTP，因此已经提出这些酶切割特异性底物以产生整联蛋白结合配体。在以前发表的工作中，我们已经表明，神经元的活动刺激快速MMP依赖脱落的细胞间粘附分子-5（ICAM-5），突触粘附分子表达的树突端脑。我们还表明ICAM-5胞外域可以与β1整联蛋白相互作用，刺激整联蛋白依赖性的cofilin磷酸化，这是树突棘成熟和LTP发生的事件。在目前的研究中，我们研究了ICAM-5胞外结构域刺激α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体（AMPAR）依赖性神经递质传递的可能性。单细胞记录显示，ICAM-5胞外域刺激AMPA迷你兴奋性突触后电流（mEPSC）的频率增加，但幅度不增加。与生物素化和沉淀试验，我们还表明，ICAM-5胞外域刺激膜水平的GluA 1，但不是GluA 2，AMPAR亚基的增加。此外，我们观察到ICAM-5相关的GluA 1磷酸化丝氨酸845的增加。同时，ICAM-5影响沿沿着的GluA 1表面染色的增加，而不影响树突棘数量的增加。总之，这些数据与可溶性ICAM-5增加突触能传递和突触后变化（包括磷酸化增加和GluA 1的树突插入）可能起作用的可能性一致。我们认为，未来的研究是必要的，以确定是否ICAM-5是一个选择组的突触CAMs，其脱落有助于MMP依赖的学习和记忆的影响之一。
Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases that can be released from neurons in an activity dependent manner to play a role in varied forms of learning and memory. MMP inhibitors impair hippocampal long term potentiation (LTP), spatial memory, and behavioral correlates of drug addiction. Since MMPs are thought to influence LTP through a β1 integrin dependent mechanism, it has been suggested that these enzymes cleave specific substrates to generate integrin binding ligands. In previously published work, we have shown that neuronal activity stimulates rapid MMP dependent shedding of intercellular adhesion molecule-5 (ICAM-5), a synaptic adhesion molecule expressed on dendrites of the telencephalon. We have also shown that the ICAM-5 ectodomain can interact with β1 integrins to stimulate integrin dependent phosphorylation of cofilin, an event that occurs with dendritic spine maturation and LTP. In the current study, we investigate the potential for the ICAM-5 ectodomain to stimulate changes in α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) dependent glutamatergic transmission. Single cell recordings show that the ICAM-5 ectodomain stimulates an increase in the frequency, but not the amplitude, of AMPA mini excitatory post synaptic currents (mEPSCs). With biotinylation and precipitation assays, we also show that the ICAM-5 ectodomain stimulates an increase in membrane levels of GluA1, but not GluA2, AMPAR subunits. In addition, we observe an ICAM-5 associated increase in GluA1 phosphorylation at serine 845. Concomitantly, ICAM-5 affects an increase in GluA1 surface staining along dendrites without affecting an increase in dendritic spine number. Together these data are consistent with the possibility that soluble ICAM-5 increases glutamatergic transmission and that post-synaptic changes, including increased phosphorylation and dendritic insertion of GluA1, could contribute. We suggest that future studies are warranted to determine whether ICAM-5 is one of a select group of synaptic CAMs whose shedding contributes to MMP dependent effects on learning and memory.
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影响因子：
1
作者：
Conant K;Lim ST;Randall B;Maguire-Zeiss KA
通讯作者：
Maguire-Zeiss KA
影响因子：
25
作者：
Gu, Jiaping;Lee, Chi Wai;Fan, Yanjie;Komlos, Daniel;Tang, Xin;Sun, Chicheng;Yu, Kuai;Hartzell, H. Criss;Chen, Gong;Bamburg, James R.;Zheng, James Q.
通讯作者：
Zheng, James Q.
影响因子：
5.5
作者：
Emond, Michelle R.;Montgomery, Johanna M.;Madison, Daniel V.
通讯作者：
Madison, Daniel V.
影响因子：
5.3
作者：
Furutani, Yutaka;Matsuno, Hitomi;Yoshihara, Yoshihiro
通讯作者：
Yoshihara, Yoshihiro
影响因子：
2.3
作者：
Brown, Travis E.;Forquer, Melissa R.;Sorg, Barbara A.
通讯作者：
Sorg, Barbara A.