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.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

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."]
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: 25123313External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  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 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Tubulin Co-immunoprecipitation Rat supraoptic nucleus lysates 25123313
TRPV1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Tubulin Co-immunofluorescence staining Rat supraoptic nucleus lysates 25123313
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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