[1][2] Kiss-and-run differs from full fusion, where the vesicle collapses fully into the plasma membrane and is then later retrieved by a clathrin-coat-dependent process.
[3] The idea that neurotransmitter might be released in "quanta" by the fusion of synaptic vesicles with the presynaptic membrane was first introduced by Bernard Katz and Jose del Castillo in 1955, when the first EM images of nerve terminals first appeared.
The possibility of transient fusion and rapid retrieval of vesicle membrane was proposed by Bruno Ceccarelli in 1973, after examining in the electron microscope strongly stimulated frog neuromuscular junctions, and indirectly supported by the work of his group in the following years, using electrophysiology, electron microscopy and quick freezing techniques.
[5] The increased accumulation of partially empty secretory vesicles following secretion, observed in electron micrographs are the most compelling evidence in favor of the kiss-and-run model.
Accumulation of partially empty vesicles following secretion suggests that during the secretory process, only a portion of the vesicular contents are able to exit the cell, which could only be possible if secretory vesicles were to temporarily establish continuity with the cell plasma membrane, expel a portion of their contents, then detach and reseal.
[1][6] At low stimulation for a period of 4 hours, Ceccarelli et al. found that there was an increase in horseradish peroxidase labeled vesicles over time, and no increases in large organelles, indicative of the vesicles fusing quickly with the presynaptic membrane and then separating from it after releasing its neurotransmitters.
[1] Further studies in Ceccarelli's lab accumulated evidence on the hypothesis of transient fusion by comparing electrophysiological and morphological data.
[7] In 1993 Alvarez de Toledo and colleagues directly demonstrated the occurrence of secretory product release during the momentary opening of a transiently fusing vesicle, by combining the measurement of membrane capacitance (that monitors changes in surface area) with amperometric detection of the release of mediators.
[4] This led Fesce et al.[2] to recapitulate all the indirect evidence in favor of transient fusion and coin the term kiss-and-run.
[9] However, accumulation of partially empty vesicles following secretion strongly favors the kiss-and-run mechanism, suggesting that during the secretory process, only a portion of the vesicular contents are able to exit the cell, which could only be possible if secretory vesicles were to temporarily establish continuity with the cell plasma membrane, expel a portion of their contents, then detach and reseal.
Studies using FM1-43, an amphiphile dye inserted into the vesicles or membrane as a marker, have been instrumental in supporting kiss-and-run in hippocampal synapses.
Studies using total internal reflection fluorescence microscopy (TIRFM) in neuroendocrine PC12 cells showed that myosin II regulates fusion pore dynamics during kiss-and-run exocytosis.
[15] Over-expression of normal myosin II regulatory light chain (RLC) in mRFP (monomeric red fluorescent protein) tagged tissue and Venus-tagged brain tissue resulted in prolonged release kinetics, while over-expression of a mutant form of myosin II RLC short shortened release kinetics.