title: The PDZ-domain protein Whirlin facilitates mechanosensory signaling in mammalian proprioceptors.
abstract: Mechanoreception is an essential feature of many sensory modalities. Nevertheless, the mechanisms that govern the conversion of a mechanical force to distinct patterns of action potentials remain poorly understood. Proprioceptive mechanoreceptors reside in skeletal muscle and inform the nervous system of the position of body and limbs in space. We show here that Whirlin/Deafness autosomal recessive 31 (DFNB31), a PDZ-scaffold protein involved in vestibular and auditory hair cell transduction, is also expressed by proprioceptive sensory neurons (pSNs) in dorsal root ganglia in mice. Whirlin localizes to the peripheral sensory endings of pSNs and facilitates pSN afferent firing in response to muscle stretch. The requirement of Whirlin in both proprioceptors and hair cells suggests that accessory mechanosensory signaling molecules define common features of mechanoreceptive processing across sensory systems.
authors.affiliation: Departments of Neuroscience, and Biochemistry and Molecular Biophysics, sd382@columbia.edu tmj1@columbia.edu g.s.bewick@abdn.ac.uk.
authors.forename: Joriene C
authors.initials: JC
authors.lastname: de Nooij
authors.affiliation: Pathology and Cell Biology, Motor Neuron Center for Biology and Disease.
authors.forename: Christian M
authors.identifier: http://orcid.org/0000-0002-3996-4697
authors.initials: CM
authors.lastname: Simon
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Simon
authors.affiliation: Departments of Neuroscience, and Biochemistry and Molecular Biophysics.
authors.forename: Staceyann
authors.initials: S
authors.lastname: Doobar
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, United Kingdom, and.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.affiliation: School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, United Kingdom.
authors.forename: Robert W
authors.identifier: http://orcid.org/0000-0003-1614-6488
authors.initials: RW
authors.lastname: Banks
authors.affiliation: Pathology and Cell Biology, Neurology, Motor Neuron Center for Biology and Disease.
authors.forename: George Z
authors.initials: GZ
authors.lastname: Mentis
authors.affiliation: School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom, sd382@columbia.edu tmj1@columbia.edu g.s.bewick@abdn.ac.uk.
authors.forename: Guy S
authors.initials: GS
authors.lastname: Bewick
authors.affiliation: Departments of Neuroscience, and Biochemistry and Molecular Biophysics, Kavli Institute for Brain Science, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, sd382@columbia.edu tmj1@columbia.edu g.s.bewick@abdn.ac.uk.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D020869:Gene Expression Profiling; D006198:Hair Cells, Auditory / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009470:Muscle Spindles / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology; D009431:Neural Conduction / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014909:Wheat Germ Agglutinins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D010320:Parvalbumins; D014909:Wheat Germ Agglutinins; C477218:Whrn protein, mouse; D016875:tau Proteins
keywords: PDZ proteins; mechanoreception; muscle spindle; proprioceptors; sensory-motor control