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Interactions with PDZ proteins diversify voltage‐gated calcium channel signaling
Author(s) -
Wang Shiyi,
Cortes Constanza J.
Publication year - 2021
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24650
Subject(s) - pdz domain , postsynaptic density , microbiology and biotechnology , scaffold protein , postsynaptic potential , active zone , biology , neurotransmission , calcium signaling , synaptic vesicle , signal transduction , chemistry , neuroscience , biophysics , vesicle , biochemistry , receptor , membrane
Voltage‐gated Ca 2+ (Ca V ) channels are crucial for neuronal excitability and synaptic transmission upon depolarization. Their properties in vivo are modulated by their interaction with a variety of scaffolding proteins. Such interactions can influence the function and localization of Ca V channels, as well as their coupling to intracellular second messengers and regulatory pathways, thus amplifying their signaling potential. Among these scaffolding proteins, a subset of PDZ (postsynaptic density‐95, Drosophila discs‐large, and zona occludens)‐domain containing proteins play diverse roles in modulating Ca V channel properties. At the presynaptic terminal, PDZ proteins enrich Ca V channels in the active zone, enabling neurotransmitter release by maintaining a tight and vital link between channels and vesicles. In the postsynaptic density, these interactions are essential in regulating dendritic spine morphology and postsynaptic signaling cascades. In this review, we highlight the studies that demonstrate dynamic regulations of neuronal Ca V channels by PDZ proteins. We discuss the role of PDZ proteins in controlling channel activity, regulating channel cell surface density, and influencing channel‐mediated downstream signaling events. We highlight the importance of PDZ protein regulations of Ca V channels and evaluate the link between this regulatory effect and human disease.