RT Journal Article
SR Electronic
T1 Remodeling of the Inner Hair Cell Microtubule Meshwork in a Mouse Model of Auditory Neuropathy AUNA1
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0295-16.2016
DO 10.1523/ENEURO.0295-16.2016
VO 3
IS 6
A1 Surel, Clément
A1 Guillet, Marie
A1 Lenoir, Marc
A1 Bourien, Jérôme
A1 Sendin, Gaston
A1 Joly, Willy
A1 Delprat, Benjamin
A1 Lesperance, Marci M.
A1 Puel, Jean-Luc
A1 Nouvian, Régis
YR 2016
UL http://www.eneuro.org/content/3/6/ENEURO.0295-16.2016.abstract
AB Auditory neuropathy 1 (AUNA1) is a form of human deafness resulting from a point mutation in the 5′ untranslated region of the Diaphanous homolog 3 (DIAPH3) gene. Notably, the DIAPH3 mutation leads to the overexpression of the DIAPH3 protein, a formin family member involved in cytoskeleton dynamics. Through study of diap3-overexpressing transgenic (Tg) mice, we examine in further detail the anatomical, functional, and molecular mechanisms underlying AUNA1. We identify diap3 as a component of the hair cells apical pole in wild-type mice. In the diap3-overexpressing Tg mice, which show a progressive threshold shift associated with a defect in inner hair cells (IHCs), the neurotransmitter release and potassium conductances are not affected. Strikingly, the overexpression of diap3 results in a selective and early-onset alteration of the IHC cuticular plate. Molecular dissection of the apical components revealed that the microtubule meshwork first undergoes aberrant targeting into the cuticular plate of Tg IHCs, followed by collapse of the stereociliary bundle, with eventual loss of the IHC capacity to transmit incoming auditory stimuli.