Multiple Ca2+ sensors in secretion: teammates, competitors or autocrats?

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Regulated neurotransmitter secretion relies on calcium (Ca2+) sensors, which are C2 domain proteins.
• These sensors interact with phospholipids and SNARE complexes, mediating Ca2+-triggered release.
• Ca2+ sensors are believed to provide clamping (preventing spontaneous fusion) and activation (promoting fusion) functions.

Purpose of the Study:

• To review working models of how multiple Ca2+ sensors interact to regulate neurotransmitter release.
• To explore the roles of different Ca2+ sensors in mediating synchronous, asynchronous, and spontaneous release.
• To discuss the potential arrangement and function of multiple Ca2+ sensors in neuronal and secretory cells.

Main Methods:

• Review of existing literature on Ca2+ sensors and neurotransmitter secretion.
• Analysis of models describing sensor-promoted and sensor-clamped fusion.
• Discussion of the interplay between Ca2+ sensors and SNARE complexes.

Main Results:

• Multiple Ca2+ sensors, often coexpressed in mammals, likely interact rather than function autonomously.
• These sensors may act on a shared vesicle pool, competing for SNARE complexes.
• Such interactions could mediate distinct release patterns: synchronous, asynchronous, and spontaneous.

Conclusions:

• The complex secretory response is likely orchestrated by the cooperative action of multiple Ca2+ sensors.
• Interactions between Ca2+ sensors and SNARE complexes are crucial for both clamping and fusion.
• Understanding these sensor dynamics is key to deciphering regulated neurotransmitter release.