Hepsin and ⍺-Tectorin's Importance in Preserving the Health of the Tectorial Membrane

The Tectorial Membrane (TM) is a structure located in the inner ear, with a large role in the ability to hear. More specifically, it correctly translates the frequency of sound waves through the ear into actual sounds of words and noise, allowing for the brain to properly understand what is being heard. Because of the importance of the TM in auditory processing, the stability and health of the structure as it develops is very sensitive and could result in the loss of hearing if tempered. In a past presentation at Loyola University’s Neuroscience Seminar course, one of the biology department’s professors, Dr. Wei-Ming Yu, talked about his research that involved the role of the Transmembrane Serine Protease 1 (TMPRSS1) gene, the protein hepsin being mainly associated with hearing in the TM. Dr. Pablo Roman‐Naranjo, a professor at the University of Granada in Granada, Spain, also conducted research regarding another protein in the TECTA gene that directly works with hearing in the TM: the ⍺-tectorin protein.

Hepsin and ⍺-tectorin are 2 very different proteins, however, when it comes to their mutations, it can affect the TM’s development and result in the loss of hearing, as well as other symptoms/disorders. With the mutation of ⍺-tectorin, the TECTA gene is unable to work to its proper functions, resulting in vertigo episodes and sensorineural hearing loss (SNHL) (hearing loss caused by damage to inner ear, brain, or the auditory nerve–also one of the most common causes amongst those with hearing-impairment), both of these symptoms being directly associated with Meniere’s Disease (MD). MD is an ear disorder that can also involve tinnitus (ear-ringing) and physical health (nausea/vomit, sound sensitivity, headaches, etc.).

 Hepsin’s mutation primarily alters the morphogenesis and hearing ability of the TM, but can also result in an inability to properly balance. Dr. Yu’s study involved the use of human hespin and the protease-dead mutant of hespin with some genetic modification of the protein in “knock-out” (KO) mice, as a means to understand what functions of hespin are needed to improve the functionality of hearing. In the results, the KO mice with human hespin had a significant increase in their hearing ability and an improvement in the overall structure of the TM, while the mice with the hespin mutant had zero improvement in all areas. This not only proved the great importance of the protein in the formation of the TM, but also how much of an impact the mutation had on its structure. 

In Dr. Roman‐Naranjo’s research, he and his associates studied the proteins and genes involved in the underlying cause of MD. They did this by examining the genetic heredity of over 70 families with traces of MD using data from exome sequencing. As a result, they found that there were many mutations in the TECTA gene in several of these families, which all encode the specific protein ⍺-tectorin. With this common result, the TM also ended up with a change in structure and function, causing further problems than hearing loss to those with MD. 

The molecular changes in these genes not only resulted in mutations towards the proteins they represent but also caused damage to an important sense in the human experience: hearing. While both changes in the TM can be managed with things like surgery and hearing aids, the understanding of MD and the change in the morphogenesis of TM brings about the idea and future questioning of how gene mutation therapy might correct these mutations and/or be adapted/built specifically for the stability of the TM.