Receptor Biology Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
Nat Neurosci. 2010 Mar;13(3):338-43. doi: 10.1038/nn.2488. Epub 2010 Jan 31.
Regulated exocytosis is essential for many biological processes and many components of the protein trafficking machinery are ubiquitous. However, there are also exceptions, such as SNAP-25, a neuron-specific SNARE protein that is essential for synaptic vesicle release from presynaptic nerve terminals. In contrast, SNAP-23 is a ubiquitously expressed SNAP-25 homolog that is critical for regulated exocytosis in non-neuronal cells. However, the role of SNAP-23 in neurons has not been elucidated. We found that SNAP-23 was enriched in dendritic spines and colocalized with constituents of the postsynaptic density, whereas SNAP-25 was restricted to axons. In addition, loss of SNAP-23 using genetically altered mice or shRNA targeted to SNAP-23 led to a marked decrease in NMDA receptor surface expression and NMDA receptor currents, whereas loss of SNAP-25 did not. SNAP-23 is therefore important for the functional regulation of postsynaptic glutamate receptors.
受调控的胞吐作用对于许多生物过程至关重要，许多蛋白质运输机制的组件也普遍存在。然而，也有例外，如 SNAP-25，一种神经元特异性 SNARE 蛋白，对于从突触前神经末梢释放突触小泡是必不可少的。相比之下，SNAP-23 是一种普遍表达的 SNAP-25 同源物，对于非神经元细胞的受调控的胞吐作用至关重要。然而，SNAP-23 在神经元中的作用尚未阐明。我们发现 SNAP-23 在树突棘中富集，并与突触后密度的成分共定位，而 SNAP-25 则局限于轴突。此外，使用基因改变的小鼠或针对 SNAP-23 的 shRNA 来消除 SNAP-23，导致 NMDA 受体表面表达和 NMDA 受体电流明显减少，而消除 SNAP-25 则没有。因此，SNAP-23 对于突触后谷氨酸受体的功能调节很重要。
