Clustering of CaV1.3 L ‐type calcium channels by Shank3

Clustering of L-type voltage-gated Ca2+ channels (LTCCs) in the plasma membrane is increasingly implicated in creating highly localized Ca2+ signaling nanodomains. Left panel: Our data support the clustering of multiple CaV1.3L L-type calcium channels by the neuronal scaffolding protein Shank3 via direct interaction of the Shank3 PDZ domain with the C-terminal domain of CaV1.3L under basal conditions. Right panel: Ca2+ influx via CaV1.3L causes disassociation of Shank3 from CaV1.3L, disrupting Shank3-mediated clustering of CaV1.3L channels. Shank3-mediated CaV1.3L clustering under basal conditions may have a key role in downstream signaling, such as excitation-transcription coupling and neuronal plasticity. AbstractClustering of L-type voltage-gated Ca2+ channels (LTCCs) in the plasma membrane is increasingly implicated in creating highly localized Ca2+ signaling nanodomains. For example, neuronal LTCC activation can increase phosphorylation of the nuclear CREB transcription factor by increasing Ca2+ concentrations within a nanodomain close to the channel, without requiring bulk Ca2+ increases in the cytosol or nucleus. However, the molecular basis for LTCC clustering is poorly understood. The postsynaptic scaffolding protein Shank3 specifically associates with one of the major neuronal LTCCs, the CaV1.3 calcium channel, and is required for optimal LTCC-dependent excitation-transcription coupling. Here, we co-expressed CaV1.3 α1 subunits with two distinct epitope-tags with...

Source: Journal of Neurochemistry - July 1, 2023 Category: Neuroscience Authors: Qian Yang, Tyler L. Perfitt, Juliana Quay, Lan Hu, Dorian Lawson ‐Qureshi, Roger J. Colbran Tags: ORIGINAL ARTICLE Source Type: research