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肌球蛋白 Va 依赖的海马神经元中 NMDA 受体的运输。

Myosin Va-dependent Transport of NMDA Receptors in Hippocampal Neurons.

机构信息

Ministry of Education (MOE) Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, 210096, China.

Department of Neurobiology, Nanjing Medical University, Nanjing, 210096, China.

出版信息

Neurosci Bull. 2024 Aug;40(8):1053-1075. doi: 10.1007/s12264-023-01174-y. Epub 2024 Jan 30.

DOI:10.1007/s12264-023-01174-y
PMID:38291290
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11306496/
Abstract

N-methyl-D-aspartate receptor (NMDAR) trafficking is a key process in the regulation of synaptic efficacy and brain function. However, the molecular mechanism underlying the surface transport of NMDARs is largely unknown. Here we identified myosin Va (MyoVa) as the specific motor protein that traffics NMDARs in hippocampal neurons. We found that MyoVa associates with NMDARs through its cargo binding domain. This association was increased during NMDAR surface transport. Knockdown of MyoVa suppressed NMDAR transport. We further demonstrated that Ca/calmodulin-dependent protein kinase II (CaMKII) regulates NMDAR transport through its direct interaction with MyoVa. Furthermore, MyoVa employed Rab11 family-interacting protein 3 (Rab11/FIP3) as the adaptor proteins to couple themselves with NMDARs during their transport. Accordingly, the knockdown of FIP3 impairs hippocampal memory. Together, we conclude that in hippocampal neurons, MyoVa conducts active transport of NMDARs in a CaMKII-dependent manner.

摘要

N-甲基-D-天冬氨酸受体（NMDAR）转运是调节突触效能和大脑功能的关键过程。然而，NMDAR 表面转运的分子机制在很大程度上尚不清楚。在这里，我们鉴定出肌球蛋白 Va（MyoVa）是在海马神经元中转运 NMDAR 的特异性运动蛋白。我们发现 MyoVa 通过其货物结合域与 NMDAR 结合。这种结合在 NMDAR 表面转运过程中增加。MyoVa 的敲低抑制了 NMDAR 的转运。我们进一步证明 Ca/钙调蛋白依赖性蛋白激酶 II（CaMKII）通过其与 MyoVa 的直接相互作用来调节 NMDAR 的转运。此外，MyoVa 利用 Rab11 家族相互作用蛋白 3（Rab11/FIP3）作为衔接蛋白，在其转运过程中将自身与 NMDAR 连接。因此，FIP3 的敲低会损害海马体记忆。总之，我们的结论是，在海马神经元中，MyoVa 以 CaMKII 依赖的方式进行 NMDAR 的主动转运。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/0b856090e0ce/12264_2023_1174_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/36232d0ff909/12264_2023_1174_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/66a876a43a28/12264_2023_1174_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/5218a9582a56/12264_2023_1174_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/ef136d561545/12264_2023_1174_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/c3ec33b49687/12264_2023_1174_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/68455759b425/12264_2023_1174_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/ab025758e8f7/12264_2023_1174_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/0b856090e0ce/12264_2023_1174_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/36232d0ff909/12264_2023_1174_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/66a876a43a28/12264_2023_1174_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/5218a9582a56/12264_2023_1174_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/ef136d561545/12264_2023_1174_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/c3ec33b49687/12264_2023_1174_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/68455759b425/12264_2023_1174_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/ab025758e8f7/12264_2023_1174_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66c9/11306496/0b856090e0ce/12264_2023_1174_Fig8_HTML.jpg

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Myosin Va-dependent Transport of NMDA Receptors in Hippocampal Neurons.

Neurosci Bull. 2024-8

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[3]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Quantifying postsynaptic receptor dynamics: insights into synaptic function.

Nat Rev Neurosci. 2023-1

[2]
CaMKII: a central molecular organizer of synaptic plasticity, learning and memory.

Nat Rev Neurosci. 2022-11

[3]
Stereotaxic atlas of the infant rat brain at postnatal days 7-13.

Front Neuroanat. 2022-8-12

[4]
Trafficking of NMDA receptors is essential for hippocampal synaptic plasticity and memory consolidation.

Cell Rep. 2022-8-16

[5]
Caldendrin and myosin V regulate synaptic spine apparatus localization via ER stabilization in dendritic spines.

EMBO J. 2022-2-15

[6]
Synaptic memory requires CaMKII.

Elife. 2021-12-15

[7]
Long-term associative memory in rats: Effects of familiarization period in object-place-context recognition test.

PLoS One. 2021

[8]
Protein Kinase C-Mediated Phosphorylation and α2δ-1 Interdependently Regulate NMDA Receptor Trafficking and Activity.

J Neurosci. 2021-7-28

[9]
Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit.

Cell Rep. 2021-7-6

[10]
Illuminating Neural Circuits in Alzheimer's Disease.

Neurosci Bull. 2021-8

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