SNAP-25 modulation of calcium dynamics underlies differences in GABAergic and glutamatergic responsiveness to depolarization.
SNAP-25 is a component of the SNARE complex implicated in synaptic vesicle exocytosis. In this study, we demonstrate that hippocampal GABAergic synapses, both in culture and in brain, lack SNAP-25 and are resistant to the action of botulinum toxins type A and E, which cleave this SNARE protein. Relative to glutamatergic neurons, which express SNAP-25, GABAergic cells were characterized by a higher calcium responsiveness to depolarization. Exogenous expression of SNAP-25 in GABAergic interneurons lowered calcium responsiveness, and SNAP-25 silencing in glutamatergic neurons increased calcium elevations evoked by depolarization. Expression of SNAP-25(1-197) but not of SNAP-25(1-180) inhibited calcium responsiveness, pointing to the involvement of the 180-197 residues in the observed function. These data indicate that SNAP-25 is crucial for the regulation of intracellular calcium dynamics and, possibly, of network excitability. SNAP-25 is therefore a multifunctional protein that participates in exocytotic function both at the mechanistic and at the regulatory level.
Verderio
Claudia
C
Department of Medical Pharmacology, CNR Institute of Neuroscience, Center of Excellence for Neurodegenerative Diseases, University of Milano, Via vanvitelli 32, Milano 20129, Italy.
Pozzi
Davide
D
Pravettoni
Elena
E
Inverardi
Francesca
F
Schenk
Ursula
U
Coco
Silvia
S
Proux-Gillardeaux
Véronique
V
Galli
Thierry
T
Rossetto
Ornella
O
Frassoni
Carolina
C
Matteoli
Michela
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005333:Fetus; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; D002118:Calcium; C096326:botulinum toxin type E