Aging differentially affects multiple aspects of vesicle fusion kinetics

Area of Science:

• Cell Biology
• Neuroscience
• Biophysics

Background:

• Exocytosis, the process of vesicle release, involves fusion pore formation, but its impact on content release and regulation is unclear.
• It is unknown if full fusion and kiss-and-run exocytosis share regulatory mechanisms or if release is pore-dependent.

Purpose of the Study:

• To investigate age-associated changes in fusion pore formation and catecholamine release during exocytosis.
• To determine if vesicle size or membrane properties regulate release probability and if different fusion modes are controlled by similar mechanisms.

Main Methods:

• Amperometry was used to measure catecholamine efflux during single exocytotic events in mouse chromaffin cells at different ages (P0, 1 month, 6 months).
• Analysis included distinguishing between full fusion, fusion pore flickering (pre-spike foot, PSF), and kiss-and-run (stand alone foot, SAF) events.

Main Results:

• All three fusion modes (full fusion, PSF, SAF) showed age-associated increases in size, occurring at different developmental stages.
• Release probability of PSF or full fusion events remained constant with age, while kiss-and-run events increased.
• Age-dependent changes in membrane bending energy were observed, suggesting altered membrane elasticity or flexural rigidity.

Conclusions:

• Vesicle size does not regulate release probability; membrane properties change with age and influence exocytosis.
• Full fusion and kiss-and-run exocytosis may be regulated by distinct mechanisms, challenging the hypothesis of conserved regulatory pathways across ages.