The Intracellular C-terminus Confers Compartment-specific Targeting of Voltage-gated Ca Channels

Overview

Journal bioRxiv

Date 2024 Jan 8

PMID 38187530

Authors

Morven Chin

Pascal S Kaeser

Affiliations

Soon will be listed here.

Abstract

To achieve the functional polarization that underlies brain computation, neurons sort protein material into distinct compartments. Ion channel composition, for example, differs between axons and dendrites, but the molecular determinants for their polarized trafficking remain obscure. Here, we identify the mechanisms that target voltage-gated Ca channels (Cas) to distinct subcellular compartments. In hippocampal neurons, Ca2s trigger neurotransmitter release at the presynaptic active zone, and Ca1s localize somatodendritically. After knockout of all three Ca2s, expression of Ca2.1, but not of Ca1.3, restores neurotransmitter release. Chimeric Ca1.3 channels with Ca2.1 intracellular C-termini localize to the active zone, mediate synaptic vesicle exocytosis, and render release fully sensitive to blockade of Ca1 channels. This dominant targeting function of the Ca2.1 C-terminus requires an EF hand in its proximal segment, and replacement of the Ca2.1 C-terminus with that of Ca1.3 abolishes Ca2.1 active zone localization. We conclude that the intracellular C-termini mediate compartment-specific Ca targeting.

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