PMID:27693258

Citation	Zhang, J, Carver, CM, Choveau, FS and Shapiro, MS (2016) Clustering and Functional Coupling of Diverse Ion Channels and Signaling Proteins Revealed by Super-resolution STORM Microscopy in Neurons. Neuron 92:461-478
Abstract	The fidelity of neuronal signaling requires organization of signaling molecules into macromolecular complexes, whose components are in intimate proximity. The intrinsic diffraction limit of light makes visualization of individual signaling complexes using visible light extremely difficult. However, using super-resolution stochastic optical reconstruction microscopy (STORM), we observed intimate association of individual molecules within signaling complexes containing ion channels (M-type K(+), L-type Ca(2+), or TRPV1 channels) and G protein-coupled receptors coupled by the scaffolding protein A-kinase-anchoring protein (AKAP)79/150. Some channels assembled as multi-channel supercomplexes. Surprisingly, we identified novel layers of interplay within macromolecular complexes containing diverse channel types at the single-complex level in sensory neurons, dependent on AKAP79/150. Electrophysiological studies revealed that such ion channels are functionally coupled as well. Our findings illustrate the novel role of AKAP79/150 as a molecular coupler of different channels that conveys crosstalk between channel activities within single microdomains in tuning the physiological response of neurons.
Links	PubMed Online version:10.1016/j.neuron.2016.09.014
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:AKAP5		GO:0045161: neuronal ion channel clustering	ECO:0000314:		P		AKAP150 facilitates the formation of neuronal ion channel clusters as indicated in figures 3A-D. UniProt Nomenclature: A-kinase anchor protein 5 (AKAP5_MOUSE) Uniprot ID: D3YVF0 Organism: Mus musculus	complete CACAO 12554
MOUSE:AKAP5		GO:0043113: receptor clustering	ECO:0000314:		P		Figures 3E and 3F confirm that AKAP150 clusters with muscarinic 1 acetylcholine receptors (M1R). UniProt Nomenclature for AKAP150: A-kinase anchor protein 5 (AKAP5_MOUSE) Uniprot ID: D3YVF0 UniProt Nomenclature for M1R: Muscarinic acetylcholine receptor M1 (ACM1_MOUSE) Uniprot ID: P12657 Organism: Mus musculus	complete CACAO 12555
MOUSE:AKAP5		GO:0070073: clustering of voltage-gated calcium channels	ECO:0000315:		P		AKAP150 forms “super-clusters” of voltage-gated calcium channels (Cav1.2) as seen in Figure 7A. It’s worth noting that absence of these clusters in the AKAP150 KO mouse in Figure 7B reveals the necessity of AKAP150 to form these clusters. Uniprot Nomenclature: A-kinase anchor protein 5 (AKAP5_MOUSE) Uniprot ID: D3YVF0 Organism: Mus musculus	complete CACAO 12556
MOUSE:AKAP5		GO:0045163: clustering of voltage-gated potassium channels	ECO:0000314:		P		AKAP150 facilitates clustering of voltage-gated potassium channels which include KCNQ2, as seen in Figure 3A and Figure 6A in peripheral nervous system neurons. Uniprot Nomenclature: A-kinase anchor protein 5 (AKAP5_MOUSE) Uniprot ID: D3YVF0 Organism: Mus musculus	complete CACAO 12557
MOUSE:TRPV1		GO:0070073: clustering of voltage-gated calcium channels	ECO:0000314:		P		TRPV1 forms clusters with multiple voltage-gated calcium channels, as seen in Figure 7A, with additional detail of these calcium channel clusters seen in Figure 8C. These calcium channel clusters form only in the presence of at least one TRPV1 channel. Uniprot Nomenclature: Transient receptor potential cation channel subfamily V member 1 (TRPV1_MOUSE) Uniprot ID: Q704Y3 Organism: Mus musculus	complete CACAO 12560
MOUSE:TRPV1		GO:0045163: clustering of voltage-gated potassium channels	ECO:0000314:		P		TRPV1 forms clusters with voltage-gated potassium channels of KCNQ2, as seen in Figures 6A and 8A. Uniprot Nomenclature: Transient receptor potential cation channel subfamily V member 1 (TRPV1_MOUSE) Uniprot ID: Q704Y3 Organism: Mus musculus	complete CACAO 12563
MOUSE:KCNQ2		GO:0045163: clustering of voltage-gated potassium channels	ECO:0000314:		P		KCNQ2 forms clusters of voltage-gated potassium channels with KCNQ3, as seen in Figure 3A-D. Uniprot Nomenclature: Potassium voltage-gated channel subfamily KQT member 2 (KCNQ2_MOUSE) Uniprot ID: Q9Z351 Organism: Mus musculus	complete CACAO 12561
MOUSE:KCNQ3		GO:0045163: clustering of voltage-gated potassium channels	ECO:0000314:		P		KCNQ3 forms clusters of voltage-gated potassium channels with KCNQ2, as seen in Figure 3A-D. UniProt Nomenclature: Potassium voltage-gated channel subfamily KQT member 3 (KCNQ3_MOUSE) UniProt ID: Q8K3F6 Organism: Mus musculus	complete CACAO 12562

References

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