USH2A is a Meissner's corpuscle protein necessary for normal vibration sensing in mice and humans
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USH2A is a Meissner's corpuscle protein necessary for normal vibration sensing in mice and humans. / Schwaller, Fred; Bégay, Valérie; García-García, Gema; Taberner, Francisco J; Moshourab, Rabih; McDonald, Brennan; Docter, Trevor; Kühnemund, Johannes; Ojeda-Alonso, Julia; Paricio-Montesinos, Ricardo; Lechner, Stefan G; Poulet, James F A; Millan, Jose M; Lewin, Gary R.
In: NAT NEUROSCI, Vol. 24, No. 1, 01.2021, p. 74-81.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - USH2A is a Meissner's corpuscle protein necessary for normal vibration sensing in mice and humans
AU - Schwaller, Fred
AU - Bégay, Valérie
AU - García-García, Gema
AU - Taberner, Francisco J
AU - Moshourab, Rabih
AU - McDonald, Brennan
AU - Docter, Trevor
AU - Kühnemund, Johannes
AU - Ojeda-Alonso, Julia
AU - Paricio-Montesinos, Ricardo
AU - Lechner, Stefan G
AU - Poulet, James F A
AU - Millan, Jose M
AU - Lewin, Gary R
PY - 2021/1
Y1 - 2021/1
N2 - Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive, vibration-sensing neurons are associated with Meissner's corpuscles in the skin. In the present study, we found that USH2A, a transmembrane protein with a very large extracellular domain, was found in terminal Schwann cells within Meissner's corpuscles. Pathogenic USH2A mutations cause Usher's syndrome, associated with hearing loss and visual impairment. We show that patients with biallelic pathogenic USH2A mutations also have clear and specific impairments in vibrotactile touch perception, as do mutant mice lacking USH2A. Forepaw rapidly adapting mechanoreceptors innervating Meissner's corpuscles, recorded from Ush2a-/- mice, showed large reductions in vibration sensitivity. However, the USH2A protein was not found in sensory neurons. Thus, loss of USH2A in corpuscular end-organs reduced mechanoreceptor sensitivity as well as vibration perception. Thus, a tether-like protein is required to facilitate detection of small-amplitude vibrations essential for the perception of fine-grained tactile surfaces.
AB - Fingertip mechanoreceptors comprise sensory neuron endings together with specialized skin cells that form the end-organ. Exquisitely sensitive, vibration-sensing neurons are associated with Meissner's corpuscles in the skin. In the present study, we found that USH2A, a transmembrane protein with a very large extracellular domain, was found in terminal Schwann cells within Meissner's corpuscles. Pathogenic USH2A mutations cause Usher's syndrome, associated with hearing loss and visual impairment. We show that patients with biallelic pathogenic USH2A mutations also have clear and specific impairments in vibrotactile touch perception, as do mutant mice lacking USH2A. Forepaw rapidly adapting mechanoreceptors innervating Meissner's corpuscles, recorded from Ush2a-/- mice, showed large reductions in vibration sensitivity. However, the USH2A protein was not found in sensory neurons. Thus, loss of USH2A in corpuscular end-organs reduced mechanoreceptor sensitivity as well as vibration perception. Thus, a tether-like protein is required to facilitate detection of small-amplitude vibrations essential for the perception of fine-grained tactile surfaces.
KW - Adult
KW - Animals
KW - Extracellular Matrix Proteins/genetics
KW - Female
KW - Humans
KW - Male
KW - Mechanoreceptors/metabolism
KW - Mice
KW - Mice, Inbred CBA
KW - Mice, Knockout
KW - Mutation/genetics
KW - Schwann Cells/physiology
KW - Sensation/physiology
KW - Skin/innervation
KW - Touch/physiology
KW - Usher Syndromes/genetics
KW - Vibration
U2 - 10.1038/s41593-020-00751-y
DO - 10.1038/s41593-020-00751-y
M3 - SCORING: Journal article
C2 - 33288907
VL - 24
SP - 74
EP - 81
JO - NAT NEUROSCI
JF - NAT NEUROSCI
SN - 1097-6256
IS - 1
ER -