TY - JOUR
T1 - Regulation of synaptic vesicle recycling by calcineurin in different vesicle pools
AU - Kumashiro, Susumu
AU - Lu, Yun Fei
AU - Tomizawa, Kazuhito
AU - Matsushita, Masayuki
AU - Wei, Fan Yan
AU - Matsui, Hideki
N1 - Funding Information:
This work was supported in part by grants-in-aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology of Japan and by grants from Preventure-JST.
PY - 2005/4
Y1 - 2005/4
N2 - The synaptic vesicles keep recycling by the processes of endocytosis and exocytosis to maintain the normal synaptic transmission. The synaptic vesicles are classified as the readily releasable pool (RRP) and the reserve pool (RP). In the endocytosis process, calcineurin (CaN), a Ca2+/calmodulin- dependent protein phosphatase, has been shown to play important roles. However, it is unclear about its roles in different vesicle pools. Here, we investigated the role of CaN in the regulation of vesicle recycling in the RRP and RP. Vesicle recycling was monitored by using fluorescent dyes FM1-43 and FM4-64 in the primary cultures of hippocampal neurons. Inhibition of CaN by FK506 and cyclosporin A suppressed the endocytosis in the RP, but not in the RRP. Inhibition of CaN also restrained the exocytic process triggered by 10 Hz stimulation, but had no effect on 3-5 Hz stimulation-induced exocytosis. FK506 also reduced the total vesicle pool size in the synaptic terminals. A synthesized CaN inhibitory peptide showed the similar effects as FK506 and cyclosporin A. These results revealed a novel mechanism that CaN plays critical roles in the distinct vesicle recycling processes.
AB - The synaptic vesicles keep recycling by the processes of endocytosis and exocytosis to maintain the normal synaptic transmission. The synaptic vesicles are classified as the readily releasable pool (RRP) and the reserve pool (RP). In the endocytosis process, calcineurin (CaN), a Ca2+/calmodulin- dependent protein phosphatase, has been shown to play important roles. However, it is unclear about its roles in different vesicle pools. Here, we investigated the role of CaN in the regulation of vesicle recycling in the RRP and RP. Vesicle recycling was monitored by using fluorescent dyes FM1-43 and FM4-64 in the primary cultures of hippocampal neurons. Inhibition of CaN by FK506 and cyclosporin A suppressed the endocytosis in the RP, but not in the RRP. Inhibition of CaN also restrained the exocytic process triggered by 10 Hz stimulation, but had no effect on 3-5 Hz stimulation-induced exocytosis. FK506 also reduced the total vesicle pool size in the synaptic terminals. A synthesized CaN inhibitory peptide showed the similar effects as FK506 and cyclosporin A. These results revealed a novel mechanism that CaN plays critical roles in the distinct vesicle recycling processes.
KW - Calcineurin
KW - Endocytosis
KW - Exocytosis
KW - Readily releasable pool
KW - Reserve pool
KW - Synaptic vesicle
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U2 - 10.1016/j.neures.2004.12.018
DO - 10.1016/j.neures.2004.12.018
M3 - Article
AN - SCOPUS:14544276353
SN - 0168-0102
VL - 51
SP - 435
EP - 443
JO - Neuroscience Research
JF - Neuroscience Research
IS - 4
ER -