Liao Xiayi, Tung Chun-Yu, Krey Jocelyn F, Behnammanesh Ghazaleh, Cirilo Joseph A, Colpan Mert, Yengo Christopher M, Barr-Gillespie Peter G, Bird Jonathan E, Perrin Benjamin J
Department of Biology, Indiana University, Indianapolis, IN, USA.
Oregon Hearing Research Center, Oregon Health & Science University, Portland, OR, USA.
Nat Commun. 2025 Jul 1;16(1):5835. doi: 10.1038/s41467-025-60976-y.
Stereocilia, the actin-based mechanosensory protrusions of inner ear sensory hair cells, require precise dimensional control for proper mechanotransduction, yet the mechanisms governing actin assembly during development remain unclear. Their size and shape are determined by a stable core of long, parallel, unbranched filamentous (F-) actin. We find that during stereocilia widening, which is a key process for function and stability, newly expressed actin first integrates at the tip, then along the periphery of the core. To understand how actin assembles, we probe for globular (G-) actin, F-actin barbed ends, and pointed ends, and identify a tip-enriched population of short actin filaments. Overexpressing actin increases these filaments at the stereocilia periphery, suggesting a role in widening. In addition, the tip-localized myosins MYO3A/B and MYO15A, essential for normal growth, generate or stabilize short filaments. We propose that these short filaments are intermediates that mature into the long F-actin known to comprise the stereocilia core.
静纤毛是内耳感觉毛细胞中基于肌动蛋白的机械感觉突起,其精确的尺寸控制对于正常的机械转导至关重要,但在发育过程中控制肌动蛋白组装的机制仍不清楚。它们的大小和形状由长的、平行的、无分支的丝状(F-)肌动蛋白的稳定核心决定。我们发现,在静纤毛增宽过程中,这是功能和稳定性的关键过程,新表达的肌动蛋白首先在尖端整合,然后沿着核心的周边整合。为了了解肌动蛋白是如何组装的,我们探测球状(G-)肌动蛋白、F-肌动蛋白的带刺末端和尖端末端,并确定了一个富含短肌动蛋白丝的尖端群体。过表达肌动蛋白会增加静纤毛周边的这些细丝,表明其在增宽过程中发挥作用。此外,尖端定位的肌球蛋白MYO3A/B和MYO15A对正常生长至关重要,它们产生或稳定短细丝。我们提出,这些短细丝是成熟为已知构成静纤毛核心的长F-肌动蛋白的中间体。
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