AMPA受体介导大部分兴奋性谷氨酸突触传递，其在树突棘膜上的数量和分布调控着树突棘可塑性，但具体调控机制不明确。我们研究发现，微管切割蛋白spastin的MIT结构域通过与AMPA受体GluA1亚基C末端直接结合，促使其内化，导致树突棘幼稚化；spastin的AAA结构域的K427是类泛素化修饰位点，突变后spastin-K427R丧失微管切割功能，促进GluA1上膜，树突棘成熟。据此，我们提出spastin类泛素化修饰调控GluA1转运介导树突棘可塑性的假说。本项目拟运用分子生物学、形态学和电生理等技术，通过研究类泛素化修饰是否影响spastin与GluA1的结合，从而调节GluA1的转运，调控树突棘可塑性，易化突触传递，以期深入解析spastin类泛素化修饰调控GluA1转运介导树突棘可塑性的机制，为研究spastin突变引起的HSP伴发的认知功能障碍提供切实的科学依据。

AMPA receptor mediates most excitatory glutamate synaptic transmission, and its number and distribution on the dendritic spine membrane regulate the plasticity of dendritic spine, but the specific mechanism is not clear. In our study, we found that the MIT domain of the microtubule-severing enzyme spastin directly binds to the C-terminal of the AMPA receptor GluA1 subunit, which promotes its endocytosis and leads to the dendrite spine infantilization. The AAA domain of spastin contains the SUMO consensus sequence, mutating Lys427 to Arg (K427R) completely prevented SUMOylation of spastin. Spastin-K427R lost the microtubule-severing function and promotes the GluA1 to the membrane and dendritic spine maturation. Accordingly, we propose that SUMOylation of spastin regulates the plasticity of dendritic spine by the trafficking of GluA1. In this study, we intend to use molecular biology techniques, immunostaining and whole-cell patch clamp to study whether the SUMOylation of spastin affects the binding of spastin and GluA1, thereby regulating the trafficking of GluA1, regulating the plasticity of dendritic spines, and promotes facilitation of synaptic transmission. Answering these questions will help elucidate the role of trafficking of GluA1 on dendritic spines plasticity mediated by SUMOylation of spastin, as well as provide a scientific basis for studying the cognitive dysfunction associated with HSP caused by spastin mutation.