Investigating functions of a cilium protein in vestibular system

Project: Research project

Project Details


Cilia are microtubule (MT)-based surface projections that play vital roles in various tissues and cells. There are two kinds of cilia: (1) motile cilia that beat rhythmically to transport fluids across epithelia. (2) non-motile primary cilia that are sensory organelles gathering information about their environment. Most of the primary cilia have MTs in the ‘9+0’ configuration, while the majority of motile cilia are composed of MTs in the ‘9+2’ configuration, i.e., two central singlet MTs surrounded by nine doublets MTs. Defective ciliary function results in multiple symptoms that are collectively referred to as ciliopathies. Recently, we discovered that a knockdown mouse model for MT minus-end regulator, CAMSAP3, exhibited Primary Ciliary Dyskinesia (PCD), a condition caused by motile ciliary defects. Our data further suggest that CAMSAP3 is needed to form central MT pairs in motile cilia on multiciliated cells (MCCs). The MT-based cytoskeleton, known as the axoneme, contains a central MT pair that is critical for the generation of a coordinated, directional flow allowing for mucus clearance in MCCs. Unlike most primary cilia, kinocilia on vestibular hair cells have a ‘9+2’ configuration. The function of this central MT pair in vestibular kinocilia remains unknown. We hypothesize that CAMSAP3 is also a critical component for these primary cilia that naturally carry MTs in the ‘9+2’ configuration, i.e., CAMSAP3 is needed to build the central MT pair in kinocilia on vestibular hair cells. Specifically, we predict that the central MT pair in vestibular kinocilia is essential to establish the long and stable cilia required for vestibular function. Hence, we propose to investigate the role of CAMSAP3 using conditional knockout mouse models specific to the inner ear. By combining the data from in vivo vestibular functional evaluations and utricular organ cultures, we will test our hypotheses by addressing the following questions: 1) Determine whether CAMSA
Effective start/end date1/1/2012/31/21


  • American Hearing Research Foundation (Letter 12/4/19)


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.