Mechanism of action of rab3A in mossy fiber LTP.
In mossy fiber synapses of the hippocampal CA3 region, LTP is induced by cAMP and requires the synaptic vesicle protein rab3A. In contrast, CA1-region synapses do not exhibit this type of LTP. We now show that cAMP enhances glutamate release from CA3 but not CA1 synaptosomes by (1) increasing the readily releasable pool as tested by hypertonic sucrose; (2) potentiating release evoked by KCl depolarization, which opens voltage-gated Ca2+ channels; and (3) by enhancing Ca2+ action on the secretory apparatus as monitored by the Ca2+-ionophore ionomycin. In rab3A-deficient synaptosomes, forskolin still enhances KCl- and sucrose-induced glutamate release but not ionomycin-induced release. Our results show that cAMP has multiple actions in mossy fiber synapses, of which only the direct activation of the secretory apparatus requires rab3A and functions in mfLTP.
Lonart
G
G
Center for Basic Neuroscience, The Department of Molecular Genetics, Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas 75235, USA.
Janz
R
R
Johnson
K M
KM
Südhof
T C
TC
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins
D005576:Colforsin; D018698:Glutamic Acid; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins