Synaptotagmin I and IX function redundantly in controlling fusion pore of large dense core vesicles.
Synaptotagmins (Syts) constitute a large family of at least 16 members and individual Syt isoforms exhibit distinct Ca(2+)-binding properties and subcellular localization. It remains to be demonstrated whether multiple Syt isoforms can function independently or cooperatively on certain type of vesicle. In the current study, we have developed NPY-pHluorin to specifically assess exocytosis of large dense core vesicles (LDCVs) and studied the requirement of Syt I and Syt IX for LDCV exocytosis in PC12 cells. We found that down-regulation of both Syt I and Syt IX resulted in a significant loss of Ca(2+)-dependent LDCV exocytosis. Moreover, our results suggest Syt I and Syt IX play redundant role in controlling the choice of fusion modes. Down-regulation of both Syt I and Syt IX renders more fusion in the kiss-and-run mode. We conclude that Syt I and Syt IX function redundantly in Ca(2+)-sensing and fusion pore dilation on LDCVs in PC12 cells.
Key Laboratory of Molecular Biophysics (Huazhong University of Science and Technology), Ministry of Education, and Joint Laboratory of Institute of Biophysics, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Dan
D
Zhu
Wei
W
Zhou
Tao
T
Liang
Fan
F
Yang
Rong-Ying
RY
Zhang
Zheng-Xing
ZX
Wu
Tao
T
Xu
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D005089:Exocytosis; D008561:Membrane Fusion; D016716:PC12 Cells; D034622:RNA Interference; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*; D050863:Synaptotagmin I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D050857:Synaptotagmins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D002395:Catecholamines; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; C483193:Syt9 protein, rat; D050857:Synaptotagmins