Novel Cytoskeleton Ultrastructures Identified

ON2019-04-20TAG: ShanghaiTech UniversityCATEGORY: School of Life Science and Technology

Recently, a research group led by iHuman Institute and SLST Assistant Professor Zhong Guisheng, working with collaborators SLST Assistant Professor He Shuijin and Southeast University Professor Chai Renjie, used a super-resolution fluorescence microscope to identify novel cytoskeleton ultrastructures in inner ear hair cell. Their two studies, “A cytoskeleton structure revealed by super-resolution fluorescence imaging in inner ear hair cells” and “Critical role of spectrin in hearing development and deafness”, were published in Cell Discovery (Feb 19, 2019) and online in Science Advances (Apr 18, 2019).

Hearing loss is the most common sensory disorder worldwide. Over 6.8% of the global population (around 500 million people) suffer from disabling hearing loss and no efficient treatment is yet available. Hair cell dysfunction is one of the most common genetic causes of hearing loss.

The cuticular plate of hair cells (HCs) is thought to be critical in mammalian hearing by securing stereocilia rootlets in place and providing them with the rigidity and support necessary for auditory transduction. Stereocilia rootlets are electron-dense structures penetrating into the cuticular plate and forming an anchoring complex. This anchoring complex is believed to be the key structural component for stereocilia to withstand constant mechanical stresses, and thus plays a critical role in hearing. However, the specific anchoring molecules that provide stereocilia rootlets with their necessary elasticity and flexibility remains elusive to researchers.

By utilizing stimulated emission depletion (STED) imaging and multiple approaches, the novel ring-like structures of spectrin, have been revealed for the first time, wrapping around the base of stereocilia rootlets. These spectrin rings were found to be closely associated with the hearing ability of mice. HC-specific, βII-spectrin knockout mice displayed profound deafness.

Fig 1. STED reveals ultrastructures of βII-spectrin in inner hair cells

Fig 2. Super-resolution facilities at imaging platform of iHuman institute

Fig 3. βII-spectrin rings disrupted in the hair cells of aging mice and noise-exposed mice

Further studies have characterized a previously unknown F-actin nanoscale structure in the cuticular plate with structured illumination microscopy (SIM) imaging. Such spatial organization of F-actin in cuticular plate may also play a critical role in hearing function.

Dr. Zhong Guisheng and his research team have long been committed to studies in the nanostructure of cytoskeleton proteins. The current work for the first time revealed ultrastructures of critical cytoskeletons in inner ear hair cells, and would greatly enhance our understanding of the ultra-structure of cuticular plate and its essential role in hearing development.

Fig. 5 Research team members of iHuman institute, ShanghaiTech University

Key co-authors of these papers include Research Assistant Professor Liu Yan, doctoral students Qi Jieyu and Chen Xin. Assistant Professor Zhong Guisheng, Professor Chai Renjie and Assistant Professor He Shuijin are co-corresponding authors. Julie Liu created the cover illustration.