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
Rok vydání: 2016
Předmět:
Zdroj: Neuron. 92:461-478
ISSN: 0896-6273
DOI: 10.1016/j.neuron.2016.09.014
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