兴奋性突触由突触前神经元的轴突扣结与突触后神经元树突上的膜突起树突棘构成。突触可塑性是神经元细胞响应神经活性变化而调节其突触强度的特性。突触可塑性的产生依赖于突触蛋白如递质受体的转运。作为兴奋性突触的主要接收位点，树突棘的结构和功能可塑性依赖于树突中的囊泡运输及囊泡-质膜相互作用。然而树突中神经活性对膜运输的调控机制尚未阐明。先前我们发现，动力蛋白dynein-dynactin的介导因子SNX6通过介导突触支架蛋白Homer1b/c的囊泡运输参与维持树突棘的结构和功能。最近我们发现，突触可塑性的经典形式长时程突触增强需要SNX6活性，而且SNX6与递质受体AMPAR及可塑性核心调控蛋白CaMKII相互作用，提示SNX6介导AMPAR转运并受到神经活性调控。我们拟运用生化、细胞和神经生物学手段，探讨SNX6-CaMKII互作对于AMPAR靶向运输的调控作用，解析神经活性调控膜运输的分子机制。

The excitatory synapse is composed of axonal boutons of presynaptic neurons and dendritic spines, membrane protrusions emanating from the plasma membrane of postsynaptic dendrites. Synaptic plasticity is modulation of synaptic strength in response to changes in neural activity. The induction and expression of synaptic plasticity relies on translocation of synaptic proteins between their site of synthesis and synaptic sites. In the central nervous system, dendritic spines are major sites for excitatory inputs. Although the structural and functional plasticity of spines rely heavily on vesicular transport and vesicle-plasma membrane interactions in dendrites, the mechanisms underlying neural activity-dependent membrane trafficking remain to be explored. Previously we found that SNX6 mediates dynein-dynactin-driven vesicular transport of the postsynaptic scaffold protein Homer1b/c, which is critical for the structural and functional integrity of dendritic spines. Most recently we found that SNX6 is also required for long-term potentiation (LTP), a classic form of synaptic plasticity. We also found that SNX6 interacts with both the glutamate receptor AMPAR, the key molecule that determines synaptic strength, and CaMKII, the master regulator of LTP. In order to investigate the molecular mechanisms for neural activity-dependent membrane trafficking in dendrites, we propose to employ biochemical, cell biological and neurobiological approaches to determine the role of SNX6-CaMKII interaction in regulation of translocation of the neurotransmitter receptor AMPAR to postsynaptic sites.