USH2A is a Meissner’s corpuscle protein necessary for normal vibration sensing in mice and humans
Fred Schwaller1, Valérie Bégay1, Gema García-García2,3, Francisco J. Taberner4,7, Rabih Moshourab 1,5,8,
Brennan McDonald1, Trevor Docter1,9, Johannes Kühnemund1, Julia Ojeda-Alonso1,
Ricardo Paricio-Montesinos 1,6, Stefan G. Lechner4, James F. A. Poulet 1,6, Jose M. Millan 2,3 and
Gary R. Lewin 1
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.