KIBRA (KIdney/BRAin protein) regulates learning and memory and stabilizes Protein kinase Mζ.
KIBRA (KIdney/BRAin protein) regulates learning and memory and stabilizes Protein kinase Mζ.
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DOI：
10.1111/jnc.12480
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发表时间：
2014-03
影响因子：
4.7
通讯作者：
Schneider A
中科院分区：
文献类型：
--
作者：
Vogt-Eisele A;Krüger C;Duning K;Weber D;Spoelgen R;Pitzer C;Plaas C;Eisenhardt G;Meyer A;Vogt G;Krieger M;Handwerker E;Wennmann DO;Weide T;Skryabin BV;Klugmann M;Pavenstädt H;Huentelmann MJ;Kremerskothen J;Schneider A
WWC 1基因在遗传上与人类情景记忆表现相关，其产物KIBRA已被证明与非典型蛋白激酶PKM β相互作用。虽然最近受到挑战，PKM β仍然是一个候选的突触后调节记忆维持。在这里，我们表明，PKM激酶是受快速蛋白酶体降解和KIBRA是必要的和足够的，以抵消这一过程，从而稳定激酶和维持其功能的延长时间。我们定义了KIBRA上的结合序列，这是一个靠近C-末端的短氨基酸基序。海马敲除大鼠中的KIBRA和小鼠中的KIBRA敲除均导致空间记忆任务中的学习和记忆表现降低，这支持了KIBRA是情景记忆中的参与者的观点。有趣的是，记忆力下降伴随着PKM β蛋白水平的下降。我们推测KIBRA稳定突触PKM β蛋白水平可能是KIBRA维持记忆的机制之一。
The WWC1 gene has been genetically associated with human episodic memory performance, and its product KIBRA has been shown to interact with the atypical protein kinase PKMζ. Although recently challenged, PKMζ remains a candidate postsynaptic regulator of memory maintenance. Here we show that PKMζ is subject to rapid proteasomal degradation and that KIBRA is both necessary and sufficient to counteract this process, thus stabilizing the kinase and maintaining its function for a prolonged time. We define the binding sequence on KIBRA, a short amino acid motif near the C-terminus. Both hippocampal knock-down of KIBRA in rats and KIBRA knock-out in mice result in decreased learning and memory performance in spatial memory tasks supporting the notion that KIBRA is a player in episodic memory. Interestingly, decreased memory performance is accompanied by decreased PKMζ protein levels. We speculate that the stabilization of synaptic PKMζ protein levels by KIBRA may be one mechanism by which KIBRA acts in memory maintenance.
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影响因子：
9.8
作者：
Serrano, Peter;Friedman, Eugenia L.;Kenney, Jana;Taubenfeld, Stephen M.;Zimmerman, Joshua M.;Hanna, John;Alberini, Cristina;Kelley, Ann E.;Maren, Stephen;Rudy, Jerry W.;Yin, Jerry C. P.;Sacktor, Todd C.;Fenton, Andre A.
通讯作者：
Fenton, Andre A.
影响因子：
6.1
作者：
Hongpaisan, Jarin;Xu, Changqing;Alkon, Daniel L.
通讯作者：
Alkon, Daniel L.
影响因子：
4.8
作者：
Hernandez, AI;Blace, N;Sacktor, TC
通讯作者：
Sacktor, TC
影响因子：
4.8
作者：
Balendran, A;Biondi, RM;Alessi, DR
通讯作者：
Alessi, DR
影响因子：
56.9
作者：
Papassotiropoulos, Andreas;Stephan, Dietrich A.;de Quervain, Dominique J. -F.
通讯作者：
de Quervain, Dominique J. -F.