Inhibition of hippocampal synaptic transmission by impairment of Ral function.
Large clostridial cytotoxins and protein overexpression were used to probe for involvement of Ras-related GTPases (guanosine triphosphate) in synaptic transmission in cultured rat hippocampal neurons. The toxins TcdA-10463 (inactivates Rho, Rac, Cdc42, Rap) and TcsL-1522 (inactivates Ral, Rac, Ras, R-Ras, Rap) both inhibited autaptic responses. In a proportion of the neurons (25%, TcdA-10463; 54%, TcsL-1522), the inhibition was associated with a shift from activity-dependent depression to facilitation, indicating that the synaptic release probability was reduced. Overexpression of a dominant negative Ral mutant, Ral A28N, caused a strong inhibition of autaptic responses, which was associated with a shift to facilitation in a majority (80%) of the neurons. These results indicate that Ral, along with at least one other non-Rab GTPase, participates in presynaptic regulation in hippocampal neurons.
Owe-Larsson
Björn
B
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Chaves-Olarte
Esteban
E
Chauhan
Ashok
A
Kjaerulff
Ole
O
Brask
Johan
J
Thelestam
Monica
M
Brodin
Lennart
L
Löw
Peter
P
D000409:Alanine / Q000235:genetics; D000818:Animals; D029681:Arabidopsis Proteins / Q000494:pharmacology; D001216:Asparagine / Q000235:genetics; D001427:Bacterial Toxins / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002247:Carbon Isotopes / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004768:Enterotoxins / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009154:Mutation / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014118:Toxins, Biological / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D020725:ral GTP-Binding Proteins / Q000502:physiology*
D029681:Arabidopsis Proteins; D001427:Bacterial Toxins; D002247:Carbon Isotopes; D004768:Enterotoxins; D018690:Excitatory Amino Acid Agonists; C109821:TSCL protein, Arabidopsis; D014118:Toxins, Biological; C041348:tcdA protein, Clostridium difficile; D005680:gamma-Aminobutyric Acid; D001216:Asparagine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D020725:ral GTP-Binding Proteins; D005947:Glucose; D000409:Alanine