Figure 2. Recent work supports a model where the vesicle-associated SNARE VAMP4 functionally diverges from the key vesicular SNARE syb2 and predominantly maintains asynchronous release. Experiments using a combination of electrophysiology and optical imaging indicate that a small but significant population of vesicles appears to be enriched in VAMP4, follows a distinct route of stimulation-dependent trafficking facilitated by VAMP4's N-terminal di-leucine motif and selectively supports asynchronous release. According to this model, sustained activity can generate a synaptic vesicle population enriched in VAMP4. A VAMP4-dependent SNARE complex formed after recruitment of these vesicles provides a substrate upon which a Ca²⁺ sensor acts to drive asynchronous release.