CAMDI interacts with the human memory-associated protein KIBRA and regulates AMPAR cell surface expression and cognition
CAMDI interacts with the human memory-associated protein KIBRA and regulates AMPAR cell surface expression and cognition
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DOI：
10.1371/journal.pone.0224967
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发表时间：
2019-11-15
期刊：
影响因子：
3.7
通讯作者：
Yanagi, Shigeru
中科院分区：
文献类型：
--
作者：
Fukuda, Toshifumi;Nagashima, Shun;Yanagi, Shigeru
人们对精神疾病认知缺陷的分子机制知之甚少。 CAMDI 是一种精神疾病相关因子，小鼠缺乏该因子会导致神经元迁移延迟和精神异常行为。在这里，我们发现 CAMDI 缺陷的小鼠表现出识别记忆和空间参考记忆受损。海马神经元中 CAMDI 的敲低增加了内化的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体 (AMPAR) 的数量，并减弱了 AMPAR 的化学长时程增强 (LTP) 依赖性细胞表面表达。 KIBRA 被鉴定为一种新型 CAMDI 结合蛋白，在内化后将 AMPAR 保留在细胞质中。 KIBRA 抑制 CAMDI 依赖性 Rab11 激活，从而减弱 AMPAR 细胞表面表达。这些结果表明 CAMDI 在 LTP 期间调节 AMPAR 细胞表面表达。 CAMDI 功能障碍可能部分解释了精神疾病认知缺陷的机制。
Little is known about the molecular mechanisms of cognitive deficits in psychiatric disorders. CAMDI is a psychiatric disorder-related factor, the deficiency of which in mice results in delayed neuronal migration and psychiatrically abnormal behaviors. Here, we found that CAMDI-deficient mice exhibited impaired recognition memory and spatial reference memory. Knockdown of CAMDI in hippocampal neurons increased the amount of internalized alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) and attenuated the chemical long-term potentiation (LTP)-dependent cell surface expression of AMPAR. KIBRA was identified as a novel CAMDI-binding protein that retains AMPAR in the cytosol after internalization. KIBRA inhibited CAMDI-dependent Rab11 activation, thereby attenuating AMPAR cell surface expression. These results suggest that CAMDI regulates AMPAR cell surface expression during LTP. CAMDI dysfunction may partly explain the mechanism underlying cognitive deficits in psychiatric diseases.