Nature：哺乳动物内耳中“端部联结”的构造
生物谷报道：内耳的毛细胞之所以被这么称呼，是因为有毛一样的东西（立纤毛）从它们的顶部表面伸出。由声音诱导的立纤毛运动，被认为是通过将立纤毛彼此连接起来的“端部联结”（tip links）与机电传导通道耦合在一起的。现在，Kazmierczak等人报告了哺乳动物“端部联结”的构造。它们是由钙依赖型细胞黏附蛋白家族的两个成员cadherin 和protocadherin 15之间的相互作用形成的。有趣的是，这些cadherins的突变引起人失聪，而且这样一个突变破坏了两个分子之间的相互作用。
原始出处:
Nature 449, 87-91 (6 September 2007) | doi:10.1038/nature06091; Received 17 April 2007; Accepted 10 July 2007
Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells
Piotr Kazmierczak1,2,4, Hirofumi Sakaguchi3,4, Joshua Tokita3, Elizabeth M. Wilson-Kubalek1, Ronald A. Milligan1, Ulrich Müller1,2,4 & Bechara Kachar3,4
- The Scripps Research, Institute Department of Cell Biology,
- Institute for Childhood and Neglected Disease, La Jolla, California 92037, USA
- Laboratory of Cellular Biology, National Institute on Deafness and other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA
- These authors contributed equally to this work.
Correspondence to: Ulrich Müller1,2,4Bechara Kachar3,4 Correspondence and requests for materials should be addressed to U.M. (Email: umueller@scripps.edu) or B.K. (Email: kacharb@nidcd.nih.gov).
Hair cells of the inner ear are mechanosensors that transduce mechanical forces arising from sound waves and head movement into electRochemical signals to provide our sense of hearing and balance. Each hair cell contains at the apical surface a bundle of stereocilia. Mechanoelectrical transduction takes place close to the tips of stereocilia in proximity to extracellular tip-link filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel1, 2, 3. Recent reports on the composition4, 5, 6, 7, 8, properties and function9, 10, 11 of tip links are conflicting29. Here we demonstrate that two cadherins that are linked to inherited forms of deafness in humans12, 13, 14, 15 interact to form tip links. Immunohistochemical studies using rodent hair cells show that cadherin 23 (CDH23) and protocadherin 15 (PCDH15) localize to the upper and lower part of tip links, respectively. The amino termini of the two cadherins co-localize on tip-link filaments. Biochemical experiments show that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affect tip-link integrity and a mutation in PCDH15 that causes a recessive form of deafness16 disrupt interactions between CDH23 and PCDH15. Our studies define the molecular composition of tip links and provide a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15.
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