Calcium Channels and SNARE Proteins

Presynaptic Ca²⁺ entry occurs through voltage-gated Ca²⁺ channels (VGCCs) which are opened by membrane depolarization, induced by action potential (AP). Ca²⁺ influx triggers neurotransmitter release from synaptic vesicles at the active zone of the presynaptic terminal. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNAREs) complex and Ca²⁺ channels involve vesicles fusion and neurotransmitter releases and their interaction and regulation have been at the forefront of neuroscience research.

Diversity of Ca²⁺ Channels in Neurons System

A variety of calcium channel types are expressed in neurons, displaying different biological structures and distribution, as well as serving a multitude of physiological roles. The diversity of channels corroborates its different physiological functions. Voltage-gated calcium channels can be broadly classified into high and low-voltage-activated channels (HVA and LVA, respectively) based on their voltage range of activation. According to the unique electrophysiological and pharmacological properties, they are also classified into N-, P/Q-, R-, L- and T-type. N-, P/Q-, R- and L-type is termed as HVA channel, while T-type is LVA channel.

Fig.1 Ca²⁺ channel structure, organization, and interaction with regulatory proteins. (He, 2018)

SNARE Proteins

SNARE proteins are a large protein family consisting of more than 60 members in mammalian cells that are critical for membrane fusion and exocytosis of neurotransmitters from the cell. Based on their functions, SNARE proteins can be classified into vesicle-SNAREs (v-SNAREs), which are associated with the vesicles and target-SNAREs (t-SNAREs), which are associated with the presynaptic plasma membrane. Synaptobrevin (vesicle-associated membrane protein family [VAMP]), syntaxin, and SNAP proteins (SNAP-25) are three main types of SNARE proteins discovered in early biochemical studies. In exocytosis/neurosecretion, SNAREs play a critical role in vesicle docking, priming, fusion and synchronization of neurotransmitter release.

Fig.2 Overview of the interaction of SNARE proteins with vesicles during exocytosis.

Interaction of Ca²⁺ Channel and SNARE Proteins Complex

Ca²⁺ entry through Ca²⁺ channel triggers vesicle fusion by the assembly of the SNARE proteins complex (syntaxin-1, SNAP-25, and VAMP). Vesicle fusion is a highly ordered process, including the following steps: 1) synaptic vesicle recruiting to active zone; 2) synaptic vesicle docking at the presynaptic membrane and with SNAREs complex conformation; 3) priming of synaptic vesicle on the presynaptic membrane; and 4) fusion pore to open and with neurotransmitter release.

Fig.3 Molecular model of a synaptic vesicle fusion machinery, interactions of active zone proteins, presynaptic Ca²⁺ channel and SNAREs. (He, 2018)

Ca²⁺ channels regulate the open/close of Ca²⁺ channels through direct binding and indirect activation of active zone proteins and SNAREs proteins. They play essential roles in the release of neurotransmitters. To better understand the structure, function and regulation of Ca²⁺ channels and SNAREs proteins, Creative Biolabs has developed a full line of high-quality neuroscience products, including but not limited to antibodies, proteins, cell lines, as well as customized development services. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.

Reference

1. He, R.; et al. New insights into interactions of presynaptic Calcium Channel subtypes and SNARE proteins in neurotransmitter release. Frontiers in molecular neuroscience. 2018, 11: 213.