Hanley Jonathan G, Khatri Latika, Hanson Phyllis I, Ziff Edward B
Howard Hughes Medical Institute, Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Neuron. 2002 Mar 28;34(1):53-67. doi: 10.1016/s0896-6273(02)00638-4.
AMPA receptor (AMPAR) trafficking is crucial for synaptic plasticity that may be important for learning and memory. NSF and PICK1 bind the AMPAR GluR2 subunit and are involved in trafficking of AMPARs. Here, we show that GluR2, PICK1, NSF, and alpha-/beta-SNAPs form a complex in the presence of ATPgammaS. Similar to SNARE complex disassembly, NSF ATPase activity disrupts PICK1-GluR2 interactions in this complex. Alpha- and beta-SNAP have differential effects on this reaction. SNAP overexpression in hippocampal neurons leads to corresponding changes in AMPAR trafficking by acting on GluR2-PICK1 complexes. This demonstrates that the previously reported synaptic stabilization of AMPARs by NSF involves disruption of GluR2-PICK1 interactions. Furthermore, we are reporting a non-SNARE substrate for NSF disassembly activity.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）的转运对于突触可塑性至关重要，而突触可塑性可能对学习和记忆很重要。N-乙基马来酰亚胺敏感因子（NSF）和蛋白相互作用与C激酶1（PICK1）结合AMPAR的GluR2亚基，并参与AMPAR的转运。在这里，我们表明，在存在ATPγS的情况下，GluR2、PICK1、NSF和α-/β-SNAPs形成一个复合物。与可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）复合物的拆解类似，NSF的ATP酶活性破坏了该复合物中PICK1与GluR2的相互作用。α-SNAP和β-SNAP对该反应有不同的影响。在海马神经元中过表达SNAP会通过作用于GluR2-PICK1复合物导致AMPAR转运发生相应变化。这表明，先前报道的NSF对AMPAR的突触稳定作用涉及破坏GluR2-PICK1的相互作用。此外，我们正在报道一种用于NSF拆解活性的非SNARE底物。
