Clustering and Functional Coupling of Diverse Ion Channels and Signaling Proteins Revealed by Super-resolution STORM Microscopy in Neurons
| Autor: | Mark S. Shapiro, Jie Zhang, Chase M. Carver, Frank S. Choveau |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Scaffold protein Cell signaling Calcium Channels L-Type A Kinase Anchor Proteins Fluorescent Antibody Technique TRPV Cation Channels CHO Cells Article KCNQ3 Potassium Channel Receptors G-Protein-Coupled 03 medical and health sciences Cricetulus Animals Humans KCNQ2 Potassium Channel Ion channel Neurons Microscopy Voltage-gated ion channel Chemistry Super-resolution microscopy General Neuroscience Optical Imaging Light-gated ion channel Cell biology Crosstalk (biology) Electrophysiology 030104 developmental biology Multiprotein Complexes |
| Zdroj: | Neuron. 92:461-478 |
| ISSN: | 0896-6273 |
| Popis: | 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 Ca2+, 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 super-complexes. 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 which conveys cross-talk between channel activities within single microdomains in tuning the physiological response of neurons. |
| Databáze: | OpenAIRE |
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