MORE ABOUT HKUST
University News
Academic Departments A-Z
Life@HKUST
Library
Map & Directions
Jobs@HKUST
Faculty Profiles
About HKUST

Search

More About HKUST
Home Why LIFS? Careers Contact Us
HKUST HKUST Division of Life Science
Research
FacultyResearch AreasFacilities
Education
Undergraduate
ProgramsScholarshipsCurriculumAdmissionCoursesResearch ProjectsInternshipsUndergraduate Advising TeamArticulation Pathways
Postgraduate
MPhil/PhD in Life SciencePhD Dual-degree ProgrammeMSc in BiotechnologyAdmissionCoursesSummer Camp
QA at HKUST
News & Events
NewsEvents
Home
September 30, 2019 by LIFS Editor News 0 comments

Pathogenesis of Usher syndrome, a hereditary deafness disease

Hair cell stereocilia convert mechanical signals (sound waves) into electrical signals (the opening of ion channels depolarizes cells to form receptor potentials) when hearing occurs. The structure of stereocilia is maintained by tip-link densities formed by the cadherin family. In Usher Syndrome, a hereditary deafness disease, such an arrangement of the stereocilia is disordered. Prof. Mingjie Zhang published in Cell Reports that a point mutation of Myo7a (Myosin VIIa) found in Usher syndrome patients leads to disruption of the hair cell tip-link protein complex formation through liquid-liquid phase separation. There are protein-dense regions at the upper and lower end insertion sites of the tip-link called known as the upper tip link density (UTLD) and lower tip link density (LTLD), respectively. The UTLD is composed of the proteins encoded by the three pathogenic genes of the Usher syndrome (Myo7a, Ush1c, and Ush1g).

The research team previously discovered that the microvilli on the surface of the small intestine, which are very similar to the shape of the stereocilia, also have a tip-link formed by the cadherin family.  They also discovered that these proteins and the UTLD of the stereocilia are highly homologous (Myosin VIIb, ANKS4B, and USH1C). First, the researchers decided to show that Myosin VIIb, USH1C and ANKS4B can form protein aggregates spontaneously through the phase separation mechanism under physiological conditions (low protein concentration, normal salt concentration, and pH value). The team followed up by demonstrating that the MYO7A/USH1C/USH1G complex can also undergo phases separation under the same condition proving that the UTLD protein complex in stereocilia uses the same mechanism to form protein aggregates. 

Due to a large number of disease-causing point mutations in Myo7a in patients with Usher syndrome, the researchers have shown that these disease-causing point mutations all affect the occurrence of phase separation, which may lead to disorganization of the UTLD in stereocilia. This explains the disease pathogenesis of Usher’s syndrome and provides potential therapeutic targets in the future.

Journal Reference:

He Y, Li J, Zhang M. Myosin VII, USH1C, and ANKS4B or USH1G Together Form Condensed Molecular Assembly via Liquid-Liquid Phase Separation. Cell Rep. 2019 Oct 22;29(4):974-986.e4. doi: 10.1016/j.celrep.2019.09.027.

brush border microvilli liquid-liquid phase separation membrane organelle publication research stereocilia tip link density Usher syndrome
1

Related Posts

Scientists reveal the molecular mechanism of Microprocessor in Caenorhabditis elegans

January 31, 2023
Read More

HKUST Receives HK$100 million Donation from Lo Kwee Seong Foundation to Advance Frontiers of Knowledge of Life Science

September 6, 2018
Read More

Relationship between Dek and Intron retention during muscle stem cells quiescence

January 20, 2021
Read More

HKUST and Pangu BioPharma (an aTyr Pharma Subsidiary) recognized for pioneering work leading to new investigational therapeutic for lung disease

January 18, 2019
Read More

Target binding mechanisms governing the WW domain-containing proteins decodedPrevious Post
Dr. Jiguang Wang received the 2019 NSFC-Excellent Young ScientistsNext Post

ADDRESS

Division of Life Science
The Hong Kong University of Science and Technology
Clear Water Bay
Kowloon, Hong Kong

PHONE

Facsimile No. :
(852) 2358 1552

Telephone No. :
(852) 2358-7272 / 7339
  • Home
  • Careers
  • Contact us
  • Faculty
  • Intranet
HKUST
PrivacySitemap
Copyright © The Hong Kong University of Science and Technology.All rights reserved.
Follow HKUST on
FacebookInstagramLinkedinYouTube
PrivacySitemap