Mechanisms controlling the trafficking, localization, and abundance of presynaptic Ca2+ channels

Karen L Cunningham; J Troy Littleton

doi:10.3389/fnmol.2022.1116729

Mechanisms controlling the trafficking, localization, and abundance of presynaptic Ca²⁺ channels

Front Mol Neurosci. 2023 Jan 13:15:1116729. doi: 10.3389/fnmol.2022.1116729. eCollection 2022.

Authors

Karen L Cunningham¹, J Troy Littleton¹

Affiliation

¹ The Picower Institute for Learning and Memory, Department of Biology, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States.

Abstract

Voltage-gated Ca²⁺ channels (VGCCs) mediate Ca²⁺ influx to trigger neurotransmitter release at specialized presynaptic sites termed active zones (AZs). The abundance of VGCCs at AZs regulates neurotransmitter release probability (P_r ), a key presynaptic determinant of synaptic strength. Given this functional significance, defining the processes that cooperate to establish AZ VGCC abundance is critical for understanding how these mechanisms set synaptic strength and how they might be regulated to control presynaptic plasticity. VGCC abundance at AZs involves multiple steps, including channel biosynthesis (transcription, translation, and trafficking through the endomembrane system), forward axonal trafficking and delivery to synaptic terminals, incorporation and retention at presynaptic sites, and protein recycling. Here we discuss mechanisms that control VGCC abundance at synapses, highlighting findings from invertebrate and vertebrate models.

Keywords: active zone; neurotransmitter release; protein trafficking; synapse; voltage-gated calcium channel.

Publication types

Review

Abstract

Publication types

Grants and funding