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.
Department of Medical Pharmacology, CNR Institute of Neuroscience, Center of Excellence for Neurodegenerative Diseases, University of Milano, Via vanvitelli 32, Milano 20129, Italy.
Claudia
C
Verderio
Davide
D
Pozzi
Elena
E
Pravettoni
Francesca
F
Inverardi
Ursula
U
Schenk
Silvia
S
Coco
Véronique
V
Proux-Gillardeaux
Thierry
T
Galli
Ornella
O
Rossetto
Carolina
C
Frassoni
Michela
M
Matteoli
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