SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Synaptic vesicle protein 2 (SV2) is a key protein in synaptic vesicles, crucial for neurotransmitter release.
• SV2 deletion in mice leads to severe epilepsy and postnatal lethality, indicating its vital role.
• The precise function of SV2 in neurotransmitter release and the exact step affected by its absence remain unclear.

Purpose of the Study:

• To elucidate the specific step in the exocytosis pathway impaired by SV2 deletion.
• To investigate the structural requirements for SV2 function in synaptic vesicle release.

Main Methods:

• Electrophysiological recordings were used to analyze neurotransmitter release dynamics in SV2-deleted synapses.
• Rescue experiments with modified SV2 constructs were performed to assess structural requirements.

Main Results:

• SV2 deletion reduced evoked synaptic responses but did not alter miniature release frequency, amplitude, vesicle pool size, or Ca(2+) sensitivity.
• Conserved charged residues in transmembrane regions and intravesicular glycosylation are essential for SV2 folding, trafficking, and function.
• The putative synaptotagmin-binding sequence of SV2 is dispensable for its role in Ca(2+) responsiveness.

Conclusions:

• SV2 acts in a maturation step that couples vesicle priming to Ca(2+) triggering of fusion.
• SV2 renders primed synaptic vesicles responsive to Ca(2+) and synaptotagmin, suggesting a role in converting vesicles to a releasable state.