BAIAP2L1 and BAIAP2L2 differently regulate hair cell stereocilia morphology

• Published in: The FASEB journal 2024-08, Vol.38 (15), p.e23860-n/a
• Main Authors: Yan, Keji, Zhang, Haoqing, Qu, Chengli, Xi, Yuehui, Han, Ze‐Guang, Xu, Zhigang
• Format: Article
• Language: English
• Subjects: Animals; BAIAP2L1; BAIAP2L2; Calcium - metabolism; F‐actin; hair cells; Hair Cells, Auditory - metabolism; Hair Cells, Auditory, Inner - metabolism; Mice; Mice, Knockout; Myosins - genetics; Myosins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; stereocilia; Stereocilia - metabolism
• ISSN: 0892-6638; 1530-6860; 1530-6860
• DOI: 10.1096/fj.202400121R

Inner ear sensory hair cells are characterized by their apical F‐actin‐based cell protrusions named stereocilia. In each hair cell, several rows of stereocilia with different height are organized into a staircase‐like pattern. The height of stereocilia is tightly regulated by two protein complexes, namely row‐1 and row‐2 tip complex, that localize at the tips of tallest‐row and shorter‐row stereocilia, respectively. Previously, we and others identified BAI1‐associated protein 2‐like 2 (BAIAP2L2) as a component of row‐2 complex that play an important role in maintaining shorter‐row stereocilia. In the present work we show that BAIAP2L1, an ortholog of BAIAP2L2, localizes at the tips of tallest‐row stereocilia in a way dependent on known row‐1 complex proteins EPS8 and MYO15A. Interestingly, unlike BAIAP2L2 whose stereocilia‐tip localization requires calcium, the localization of BAIAP2L1 on the tips of tallest‐row stereocilia is calcium‐independent. Therefore, our data suggest that BAIAP2L1 and BAIAP2L2 localize at the tips of different stereociliary rows and might regulate the development and/or maintenance of stereocilia differently. However, loss of BAIAP2L1 does not affect the row‐1 protein complex, and the auditory and balance function of Baiap2l1 knockout mice are largely normal. We hypothesize that other orthologous protein(s) such as BAIAP2 might compensate for the loss of BAIAP2L1 in the hair cells. BAI1‐associated protein 2 (BAIAP2), BAIAP2‐like 1 and 2 (BAIAP2L1 and BAIAP2L2) are orthologous I‐BAR proteins that are known to regulate cell protrusions. Here we show that BAIAP2L1 and BAIAP2L2 localize at the tips of tallest‐ and shorter‐row stereocilia of auditory hair cells, respectively, suggesting that they might regulate hair cell stereocilia differently. Loss of BAIAP2L2 results in degeneration of shorter‐row stereocilia. However, loss of BAIAP2L1 does not affect stereocilia morphology, which might be compensated for by BAIAP2.