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A presynaptic role for the ADP ribosylation factor (ARF)-specific GDP/GTP exchange factor msec7-1
- Source :
- Proceedings of the National Academy of Sciences. 96:1094-1099
- Publication Year :
- 1999
- Publisher :
- Proceedings of the National Academy of Sciences, 1999.
-
Abstract
- ADP ribosylation factors (ARFs) represent a family of small monomeric G proteins that switch from an inactive, GDP-bound state to an active, GTP-bound state. One member of this family, ARF6, translocates on activation from intracellular compartments to the plasma membrane and has been implicated in regulated exocytosis in neuroendocrine cells. Because GDP release in vivo is rather slow, ARF activation is facilitated by specific guanine nucleotide exchange factors like cytohesin-1 or ARNO. Here we show that msec7-1, a rat homologue of cytohesin-1, translocates ARF6 to the plasma membrane in living cells. Overexpression of msec7-1 leads to an increase in basal synaptic transmission at the Xenopus neuromuscular junction. msec7-1-containing synapses have a 5-fold higher frequency of spontaneous synaptic currents than control synapses. On stimulation, the amplitudes of the resulting evoked postsynaptic currents of msec7-1-overexpressing neurons are increased as well. However, further stimulation leads to a decline in amplitudes approaching the values of control synapses. This transient effect on amplitude is strongly reduced on overexpression of msec7-1E157K, a mutant incapable of translocating ARFs. Our results provide evidence that small G proteins of the ARF family and activating factors like msec7-1 play an important role in synaptic transmission, most likely by making more vesicles available for fusion at the plasma membrane.
- Subjects :
- Embryo, Nonmammalian
ADP ribosylation factor
Recombinant Fusion Proteins
Xenopus
Green Fluorescent Proteins
Neuromuscular Junction
Small G Protein
Neurotransmission
Biology
Kidney
Transfection
Exocytosis
Neuromuscular junction
Cell Line
Cell membrane
GTP-binding protein regulators
GTP-Binding Proteins
medicine
Animals
Guanine Nucleotide Exchange Factors
Humans
RNA, Messenger
Cloning, Molecular
Muscle, Skeletal
Evoked Potentials
Cells, Cultured
Neurons
Multidisciplinary
ADP-Ribosylation Factors
Cell Membrane
Brain
Proteins
Biological Sciences
Coculture Techniques
Rats
Cell biology
Kinetics
Luminescent Proteins
medicine.anatomical_structure
Synapses
Guanine nucleotide exchange factor
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....ea6186f5f6e0e692ab1c62dbac0228fe