Abl family nonreceptor tyrosine kinases modulate short-term synaptic plasticity.
Abl family nonreceptor tyrosine kinases regulate cell morphogenesis through functional interactions with the actin cytoskeleton. The vertebrate Abl family kinases, Abl and Arg, are expressed in the adult mouse brain, where they may regulate actin cytoskeletal dynamics in mature neurons. Using immunoelectron microscopy, we have localized Abl and Arg to the pre- and postsynaptic compartments of synapses in the mouse hippocampal area CA1. Paired-pulse facilitation (PPF) was significantly reduced at the Schaffer collateral-CA1 (SC-CA1) excitatory synapses in hippocampal slices from abl-/- and arg-/- mice as compared with wild-type mice. Furthermore, treatment of wild-type slices with the specific Abl family kinase inhibitor STI571 also reduced PPF. Basal synaptic transmission, posttetanic potentiation (PTP), long-term potentiation (LTP), and long-term depression (LTD) were similar to wild-type controls in abl-/- and arg-/- slices and in STI571-treated wild-type slices. These results indicate that an important function of Abl and Arg is to modulate synaptic efficacy via a presynaptic mechanism during repetitive activation.
Moresco
Eva Marie Yang
EM
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Scheetz
Alfred J
AJ
Bornmann
William G
WG
Koleske
Anthony J
AJ
Fitzsimonds
Reiko Maki
RM
D000818:Animals; D001549:Benzamides; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D000068877:Imatinib Mesylate; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D016253:Microscopy, Immunoelectron; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D010879:Piperazines / Q000494:pharmacology; D011336:Probability; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D013569:Synapses / Q000201:enzymology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology
D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl