Neuron. 2014 Aug 20;83(4):866-78. doi: 10.1016/j.neuron.2014.07.023. Epub 2014 Aug 7.
Unique interweaved microtubule scaffold mediates osmosensory transduction via physical interaction with TRPV1.
Prager-Khoutorsky, M., Khoutorsky, A., Bourque, C. W.,
["Center for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.", "Department of Biochemistry and Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.", "Center for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada. Electronic address: charles.bourque@mcgill.ca."]
["Center for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.", "Department of Biochemistry and Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.", "Center for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada. Electronic address: charles.bourque@mcgill.ca."]
The electrical activity of mammalian osmosensory neurons (ONs) is increased by plasma hypertonicity to command thirst, antidiuretic hormone release, and increased sympathetic tone during dehydration. Osmosensory transduction is a mechanical process whereby decreases in cell volume cause the activation of transient receptor potential vanilloid type-1 (TRPV1) channels to induce depolarization and increase spiking activity in ONs. However, it is not known how cell shrinking is mechanically coupled to channel activation. Using superresolution imaging, we found that ONs are endowed with a uniquely interweaved scaffold of microtubules throughout their somata. Microtubules physically interact with the C terminus of TRPV1 at the cell surface and provide a pushing force that drives channels activation during shrinking. Moreover, we found that changes in the density of these interactions can bidirectionally modulate osmosensory gain. Microtubules are thus an essential component of the vital neuronal mechanotransduction apparatus that allows the brain to monitor and correct body hydration.
PMID: 25123313
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Validation: In vivo validation
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| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPV1 |
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Tubulin | Co-immunoprecipitation | Rat supraoptic nucleus lysates | 25123313 | |||||
| TRPV1 |
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Tubulin | Co-immunofluorescence staining | Rat supraoptic nucleus lysates | 25123313 | |||||
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