Journal Club: Myosin VIIa (MYO7A) is important for stiffness of the mature stereocilia

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Today's journal article

Underhill A, Webb S, Grandi FC, Jeng JY, de Monvel JB, Plion B, Carlton AJ, Amariutei AE, Voulgari N, De Faveri F, Ceriani F, Mustapha M, Johnson SL, Safieddine S, Kros CJ, Marcotti W. MYO7A is required for the functional integrity of the mechanoelectrical transduction complex in hair cells of the adult cochlea. 

Why I picked this article

This research investigates one of the most famous proteins related to auditory hair cells - Myosin VIIa. 

The cellular "sensor" for our perception of sound is specialised cells called "hair cells". As the name suggests, auditory hair cells have a "hair" like structure called "stereocilia". When stereocilia bend, hair cells release neurotransmitters and activate auditory neurons. So, stereocilia on hair cells are the super-sensitive mechanical sensors of sound. Myosin VIIa, or MYO7A is a special protein highly abundant in both inner and outer hair cells. It has been known for some time that MYO7A is important for development and function of the stereocilia, but its exact role has not been known. 

Some of the research findings

Animal model design:

  • Transgenic mice - conditional knockout of MYO7A by Myo7afl/fl crossed with Myo15cre+/− mice.
  • In these conditional knockout mice (Myo7afl/flMyo15cre+/-), new production of MYO7a will occur on postnatal day 3 or 4 onwards in mice. This design allows the initial development of hair cells first, and then removes MYO7a to investigate the impact of missing MYO7a in stereocilia. 
  • In addition, Myo7afl/flMyo15cre+/-)mice was created with additional gene modification to remove functional TECTA protein, which is a component of the collagenous membrane called the tectorial membrane = Myo7afl/flMyo15cre+/-Tecta-/- 
  • Myo7afl/flMyo15cre+/-Tecta-/- mice have the tactorial membrane detached from the stereocilia; this enabled researchers do conduct further analysis on the stereocilia of the mice missing MYO7A. 

Effect of losing MYO7A:

  • Myo7afl/flMyo15cre+/- mice had normal hearing at 20-day-old, but developed hearing loss by 30-day-old, with evidence of some outer hair cell dysfunction. 
  • Despite the loss of functional MYO7A, the stereocilia shape and three-layered arrangement in outer hair cells looked normal. 

Stereocilia function:

  • Researchers then investigated the stereocilia functionality by bending stereocilia of outer hair cells 50Hz frequency, and measuring the ion movement (which is how stereocilia detect sounds). 
  • They observed that by around 30-day old, the ion movement in stereocilia in response to bending of stereocilia was reduced. Many features of stereocilia, like height, number, width and number of "tip-link" connecting adjacent stereocilia, or the frequency of the ion channel on the stereocilia opening ( "MET channel open probability") were the same between Myo7afl/flMyo15cre+/-Tecta-/-  and comparative control (normal) group. 
  • What was different in Myo7afl/flMyo15cre+/-Tecta-/-  was that the stiffness of the stereocilia was reduced. Similar observation was made in inner hair cells as well.
Overall, the study suggests that the MYO7A is very important for maintaining the structural stiffness of the stereocilia, but does not seem to regulate the overall shape of stereocilia or the opening of ion channels. 

From parts of Figure 3. Underhill et al. (2025)

Haruna's takeaway

This study uses a nice combination of transgenic mice to control the timing of MYO7A deficiency to focus on investigating the role of the MYO7A protein in more mature hair cells. The characterisation of stereocilia with electron microscopy looks beautiful, and it looks at the changes in stereocilia both functionally and morphologically. Individual techniques are very difficult, but the data presented in the article looks very beautiful. 

It is a very nice research about MYO7A, which gives resolution to what each protein in the stereocilia may be doing, for a certain aspect of the stereocilia physiology. Very exciting to see this study in the PNAS, one of the top physiology journals.  

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This is Haruna's 10/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.