C-terminal domain of mammalian complexin-1 localizes to highly curved membranes.
In presynaptic nerve terminals, complexin regulates spontaneous "mini" neurotransmitter release and activates Ca2+-triggered synchronized neurotransmitter release. We studied the role of the C-terminal domain of mammalian complexin in these processes using single-particle optical imaging and electrophysiology. The C-terminal domain is important for regulating spontaneous release in neuronal cultures and suppressing Ca2+-independent fusion in vitro, but it is not essential for evoked release in neuronal cultures and in vitro. This domain interacts with membranes in a curvature-dependent fashion similar to a previous study with worm complexin [Snead D, Wragg RT, Dittman JS, Eliezer D (2014) Membrane curvature sensing by the C-terminal domain of complexin. Nat Commun 5:4955]. The curvature-sensing value of the C-terminal domain is comparable to that of α-synuclein. Upon replacement of the C-terminal domain with membrane-localizing elements, preferential localization to the synaptic vesicle membrane, but not to the plasma membrane, results in suppression of spontaneous release in neurons. Membrane localization had no measurable effect on evoked postsynaptic currents of AMPA-type glutamate receptors, but mislocalization to the plasma membrane increases both the variability and the mean of the synchronous decay time constant of NMDA-type glutamate receptor evoked postsynaptic currents.
Key Laboratory of Cognitive Science, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|College of Life Science, South-Central University for Nationalities, Wuhan 430074, China.
Jihong
J
Gong
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
Ying
Y
Lai
Key Laboratory of Cognitive Science, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|College of Life Science, South-Central University for Nationalities, Wuhan 430074, China.
Xiaohong
X
Li
Key Laboratory of Cognitive Science, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|College of Life Science, South-Central University for Nationalities, Wuhan 430074, China.
Mengxian
M
Wang
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.|Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
Jeremy
J
Leitz
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Yachong
Y
Hu
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
Yunxiang
Y
Zhang
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.
Ucheor B
UB
Choi
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.|Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
Daniel
D
Cipriano
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.|Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
Richard A
RA
Pfuetzner
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305.|Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
Thomas C
TC
Südhof
Key Laboratory of Cognitive Science, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China; sunlittlefly@hotmail.com brunger@stanford.edu diaojj@gmail.com.|Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, South-Central University for Nationalities, Wuhan 430074, China.|College of Life Science, South-Central University for Nationalities, Wuhan 430074, China.
Xiaofei
X
Yang
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; sunlittlefly@hotmail.com brunger@stanford.edu diaojj@gmail.com.|Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.|Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305.|Department of Structural Biology, Stanford University, Stanford, CA 94305.|Department of Photon Science, Stanford University, Stanford, CA 94305.
Axel T
AT
Brunger
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; sunlittlefly@hotmail.com brunger@stanford.edu diaojj@gmail.com.|Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
Jiajie
0000-0003-4288-3203
J
Diao
D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D050857:Synaptotagmins / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D051844:alpha-Synuclein; C095992:complexin I; D050857:Synaptotagmins; D002118:Calcium
SNAREs; complexin; membrane fusion; neurotransmitter release; synaptic vesicle fusion