BAIAP2L2 Regulates Stereocilia Maintenance In Inner Ear Hair Cells

The inner ear of mammals consists of cochlea and vestibule,which individually includes cochlear hair cells and vestibular hair cells.Hair cells are mechanosensitive cells in the inner ear.In each hair cell,the development and maintenance of stereocilia is strictly regulated and neatly arranged in a staircase-like pattern.And the loss of stereocilia results in deafness.The mechanical-electrical transduction(MET)channel is located near the tip of the shorter row of stereocilia.In the cochlear hair cells,a so-called "Row 2 complex" is also located at the tip of the mechanotransducing stereocilia,including CAPZB2,TWF2,EPS8L2 and MYO15A-L.As is reported recently,their absences lead to the degeneration of stereocilia in mice.In our study,BAIAP2L2 is a newly discovered member of the Row 2 complex,which is located at the tip of the mechanotransducing stereocilia.We found that the deficiency of BAIAP2L2 in mice exhibits progressive deafness,degeneration of the stereocilia and the impairment of MET in cochlea.We identified the interacting proteins of BAIAP2L2,in which CAPZB2,TWF2 and EPS8L2 are known members of the Row 2 complex,and found that the localization of CAPZB2 in the stereocilia of cochlear hair cells depends on BAIAP2L2.Interestingly,BAIAP2L2 interacts with CIB2,which is a member of MET complex.And the localization of BAIAP2L2 depends on CIB2.In summary,we found that BAIAP2L2,a member of the Row 2 complex,plays a vital role in the maintenance of mechanotransducing stereocilia in cochlear hair cells.Given that the deficiency of CAPZB2,a member of the Row 2 complex,leads to vestibular dysfunction in mice,and CAPZB2 interacts with BAIAP2L2,we studied the function of BAIAP2L2 in vestibular function.In our study,we found that BAIAP2L2 is mainly located at the tip of the shorter stereocilia in the vestibular hair cells,suggesting that BAIAP2L2 plays an important role in the vestibular hair cells.We observed the morphology of vestibular hair cells in Baiap2l2-/-mice.And,surprisingly,the morphology of their stereocilia as well as the number and density of vestibular hair cells are not abnormal,and there are normal MET function in vestibular hair cells.Moreover,behavioral tests showed that the vestibular function is normal in Baiap212-/-mice.The localization of BAIAP2L2 is the same as that of CAPZB2 in the vestibular hair cell stereocilia.In the cochlear hair cells,the localization of CAPZB2 depends on BAIAP2L2.However,in the vestibular hair cells,the localization of CAPZB2 is not affected by it.Based on these data,we think that the lack of BAIAP2L2 does not affect the maintenance of stereocilia in vestibular hair cells,nor does it affect vestibular function in mice.