Taperin bundles F-actin at stereocilia pivot points enabling optimal lifelong mechanosensitivity

Authors:

Inna A. Belyantseva, Chang Liu, Abigail K. Dragich, Takushi Miyoshi, Sayaka Inagaki, Ayesha Imtiaz, Risa Tona, Karen Sofia Zuluaga-Osorio, Shadan Hadi, Elizabeth Wilson, Eva Morozko, Rafal Olszewski, Rizwan Yousaf, Yuliya Sokolova, Gavin P. Riordan, S. Andrew Aston, Atteeq U. Rehman, Cristina Fenollar Ferrer, Jan Wisniewski, Shoujun Gu, Gowri Nayak, Richard J. Goodyear, Jinan Li, Jocelyn F. Krey, Talah Wafa, Rabia Faridi, Samuel Mawuli Adadey , Meghan Drummond, Benjamin Perrin, Dennis C. Winkler, Matthew F. Starost, Hui Cheng, Tracy Fitzgerald, Guy P. Richardson, Lijin Dong, Peter G. Barr-Gillespie, Michael Hoa, Gregory I. Frolenkov, Thomas B. Friedman, Bo Zhao

Keywords:

Stereocilia; Taperin; F-actin; mechanosensitivity; TPRN; inner ear hair cell

Abstract:

Stereocilia are rod-like mechanosensory projections consisting of unidirectionally oriented actin filaments that extend into the inner ear hair cell cytoskeleton, forming dense rootlets. Taperin (TPRN) localizes to the narrowed-down base of stereocilia, where they pivot in response to sound and gravity. We show that TPRN–deficient mice have progressive deafness characterized by gradual asynchronous retraction and fusion of outer and inner hair cell stereocilia, followed by synaptic abnormalities. Stereocilia that lack TPRN develop warped rootlets with gradual loss of TRIOBP-5 and ANKRD24 from mechanosensory rows starting postnatally. In contrast, TPRN overexpression causes excessive F-actin bundling, extra rows, and over-elongation of stereocilia during development. Purified full-length mouse TPRN cross-links F-actin into bendable bundles reflecting in vivo data. This F-actin–bundling ability is attributed to the TPRN N-terminal region. TPRN interacts with the membrane receptor PTPRQ, connecting the F-actin core to the plasma membrane, stabilizing stereocilia. Thus, TPRN is a specialized F-actin bundler strategically located to augment stereocilia rootlet formation and their pivot point flexibility for sustained sound-induced deflections.

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