东南大学Lu, Wei小组取得一项新突破。他们的最新研究提出了海马神经元中肌球蛋白va依赖性NMDA受体的转运。该项研究成果发表在2024年1月30日出版的《神经科学通报》上。

研究人员发现肌球蛋白Va（MyoVa）是海马神经元中，运输N-甲基-D-天冬氨酸受体（NMDAR）的特异性运动蛋白。研究人员发现，MyoVa通过其货物结合域与NMDAR结合。在NMDAR表面运输过程中，这种结合会增强。敲除MyoVa会抑制NMDAR转运。研究人员进一步证实，钙离子/钙调蛋白依赖性蛋白激酶II（CaMKII）通过与MyoVa的直接相互作用调节NMDAR转运。

此外，MyoVa还利用Rab11家族互作蛋白3（Rab11/FIP3）作为适配蛋白，在转运过程中将自身与NMDAR耦合。因此，敲除FIP3会损害海马记忆。综上所述，研究人员得出结论：在海马神经元中，MyoVa以一种依赖于CaMKII的方式进行NMDAR的主动运输。

据了解，NMDAR的转运是调节突触功效和大脑功能的一个关键过程。然而，NMDAR表面转运的分子机制在很大程度上还不为人知。

附：英文原文

Title: Myosin Va-dependent Transport of NMDA Receptors in Hippocampal Neurons

Author: Gong, Ru, Qin, Linwei, Chen, Linlin, Wang, Ning, Bao, Yifei, Lu, Wei

Issue&Volume: 2024-01-30

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 Ca2+/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.

DOI: 10.1007/s12264-023-01174-y

Source: https://link.springer.com/article/10.1007/s12264-023-01174-y