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.

N-甲基-D-天冬氨酸受体（NMDAR）运输是调节突触功效和脑功能的关键过程。然而，NMDAR 表面传输的分子机制在很大程度上尚不清楚。在这里，我们将肌球蛋白 Va (MyoVa) 确定为在海马神经元中运输 NMDAR 的特定运动蛋白。我们发现 MyoVa 通过其货物结合域与 NMDAR 结合。这种关联在 NMDAR 表面传输期间增加。MyoVa 的敲低抑制了 NMDAR 转运。我们进一步证明Ca ²⁺ /钙调蛋白依赖性蛋白激酶II (CaMKII) 通过与MyoVa 的直接相互作用来调节NMDAR 转运。此外，MyoVa 采用 Rab11 家族相互作用蛋白 3 (Rab11/FIP3) 作为衔接蛋白，在 NMDAR 运输过程中将其自身与 NMDAR 偶联。因此， FIP3的敲低会损害海马记忆。总之，我们得出结论，在海马神经元中，MyoVa 以 CaMKII 依赖性方式主动转运 NMDAR。