Duan, SM (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China,email@example.com
Identifying the molecules that regulate both the recycling of synaptic vesicles and the SNARE components required for fusion is critical for elucidating the molecular mechanisms underlying synaptic plasticity. SNAP- 29 was initially isolated as a syntaxin- binding and ubiquitously expressed protein. Previous studies have suggested that SNAP- 29 inhibits SNARE complex disassembly, thereby reducing synaptic transmission in cultured superior cervical ganglion neurons in an activity-dependent manner. However, the role of SNAP- 29 in regulating synaptic vesicle recycling and short- term plasticity in the central nervous system remains unclear. In the present study, we examined the effect of SNAP- 29 on synaptic transmission in cultured hippocampal neurons by dual patch clamp whole- cell recording, FM dye imaging, and immunocytochemistry. Our results demonstrated that exogenous expression of SNAP- 29 in presynaptic neurons significantly decreased the efficiency of synaptic transmission after repetitive firing within a few minutes under low and moderate frequency stimulations ( 0.1 and 1 Hz). In contrast, SNAP- 29 did not affect the density of synapses and basal synaptic transmission. Whereas neurotransmitter release was unaffected during intensive stimulation, recovery after synaptic depression was impaired by SNAP- 29. Furthermore, knockdown of SNAP- 29 expression in neurons by small interfering RNA increased the efficiency of synaptic transmission during repetitive firing. These findings suggest that SNAP- 29 acts as a negative modulator for neurotransmitter release, probably by slowing recycling of the SNARE- based fusion machinery and synaptic vesicle turnover.