Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education, School of Life Sciences, Shandong University, Qingdao, Shandong, China.
Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
FASEB J. 2024 Aug 15;38(15):e23860. 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.
内耳感觉毛细胞的特征是其顶端的 F-肌动蛋白细胞突起，称为纤毛。在每个毛细胞中，几排具有不同高度的纤毛组织成阶梯状图案。纤毛的高度由两个蛋白质复合物严格调节，即第 1 排和第 2 排尖端复合物，它们分别位于最高排和较短排纤毛的尖端。以前，我们和其他人将 BAI1 相关蛋白 2 样 2（BAIAP2L2）鉴定为第 2 排复合物的一个组成部分，该复合物在维持较短排纤毛方面发挥着重要作用。在本工作中，我们表明 BAIAP2L1，BAIAP2L2 的同源物，以依赖于已知的第 1 排复合物蛋白 EPS8 和 MYO15A 的方式定位在最高排纤毛的尖端。有趣的是，与 BAIAP2L2 不同，其纤毛尖端定位需要钙，BAIAP2L1 在最高排纤毛尖端的定位是钙非依赖性的。因此，我们的数据表明 BAIAP2L1 和 BAIAP2L2 定位于不同的纤毛排，可能以不同的方式调节纤毛的发育和/或维持。然而，BAIAP2L1 的缺失并不影响第 1 排蛋白复合物，并且 Baiap2l1 敲除小鼠的听觉和平衡功能基本正常。我们假设其他同源蛋白（如 BAIAP2）可能在毛细胞中补偿 BAIAP2L1 的缺失。
