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Vol. 19, Issue 12, 5338-5346, December 2008

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Sentan: A Novel Specific Component of the Apical Structure of Vertebrate Motile Cilia

Akiharu Kubo^*, Akiko Yuba-Kubo, Sachiko Tsukita, Shoichiro Tsukita, and Masayuki Amagai^*

*Department of Dermatology, Keio University School of Medicine, Tokyo 160-8582, Japan; Mitsubishi Kagaku Institute of Life Sciences, Tokyo 194-8511, Japan; Biological Science Laboratory, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; and Department of Cell Biology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan

Submitted July 7, 2008; Revised August 11, 2008; Accepted September 24, 2008
Monitoring Editor: Francis A. Barr

Human respiratory and oviductal cilia have specific apical structures characterized by a narrowed distal portion and a ciliary crown. These structures are conserved among vertebrates that have air respiration systems; however, the molecular components of these structures have not been defined, and their functions are unknown. To identify the molecular component(s) of the cilia apical structure, we screened EST libraries to identify gene(s) that are exclusively expressed in ciliated tissues, are transcriptionally up-regulated during in vitro ciliogenesis, and are not expressed in testis (because sperm flagella have no such apical structures). One of the identified gene products, named sentan, was localized to the distal tip region of motile cilia. Using anti-sentan polyclonal antibodies and electron microscopy, sentan was shown to localize exclusively to the bridging structure between the cell membrane and peripheral singlet microtubules, which specifically exists in the narrowed distal portion of cilia. Exogenously expressed sentan showed affinity for the membrane protrusions, and a protein–lipid binding assay revealed that sentan bound to phosphatidylserine. These findings suggest that sentan is the first molecular component of the ciliary tip to bridge the cell membrane and peripheral singlet microtubules, making the distal portion of the cilia narrow and stiff to allow for better airway clearance or ovum transport.

Address correspondence to: Akiharu Kubo (akiharukubo{at}gmail.com)