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

TY - JOUR

T1 - Multiple Ca2+ sensors in secretion

T2 - teammates, competitors or autocrats?

AU - Walter, Alexander M

AU - Groffen, Alexander J

AU - Sørensen, Jakob Balslev

AU - Verhage, Matthijs

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2011/9

Y1 - 2011/9

N2 - Regulated neurotransmitter secretion depends on Ca(2+) sensors, C2 domain proteins that associate with phospholipids and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complexes to trigger release upon Ca(2+) binding. Ca(2+) sensors are thought to prevent spontaneous fusion at rest (clamping) and to promote fusion upon Ca(2+) activation. At least eight, often coexpressed, Ca(2+) sensors have been identified in mammals. Accumulating evidence suggests that multiple Ca(2+) sensors interact, rather than work autonomously, to produce the complex secretory response observed in neurons and secretory cells. In this review, we present several working models to describe how different sensors might be arranged to mediate synchronous, asynchronous and spontaneous neurotransmitter release. We discuss the scenario that different Ca(2+) sensors typically act on one shared vesicle pool and compete for binding the multiple SNARE complexes that are likely to assemble at single vesicles, to exert both clamping and fusion-promoting functions.

AB - Regulated neurotransmitter secretion depends on Ca(2+) sensors, C2 domain proteins that associate with phospholipids and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complexes to trigger release upon Ca(2+) binding. Ca(2+) sensors are thought to prevent spontaneous fusion at rest (clamping) and to promote fusion upon Ca(2+) activation. At least eight, often coexpressed, Ca(2+) sensors have been identified in mammals. Accumulating evidence suggests that multiple Ca(2+) sensors interact, rather than work autonomously, to produce the complex secretory response observed in neurons and secretory cells. In this review, we present several working models to describe how different sensors might be arranged to mediate synchronous, asynchronous and spontaneous neurotransmitter release. We discuss the scenario that different Ca(2+) sensors typically act on one shared vesicle pool and compete for binding the multiple SNARE complexes that are likely to assemble at single vesicles, to exert both clamping and fusion-promoting functions.

KW - Animals

KW - Calcium

KW - Humans

KW - Membrane Fusion

KW - Neurons

KW - Neurotransmitter Agents

KW - Protein Structure, Tertiary

KW - SNARE Proteins

KW - Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins

KW - Synapses

KW - Synaptic Transmission

KW - Synaptic Vesicles

U2 - 10.1016/j.tins.2011.07.003

DO - 10.1016/j.tins.2011.07.003

M3 - Review

C2 - 21831459

SN - 0166-2236

VL - 34

SP - 487

EP - 497

JO - Trends in Neurosciences

JF - Trends in Neurosciences

IS - 9

ER -