Sentan: a novel specific component of the apical structure of vertebrate motile cilia.
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.
Kubo
Akiharu
A
Department of Dermatology, Keio University School of Medicine, Tokyo 160-8582, Japan. akiharukubo@gmail.com
Yuba-Kubo
Akiko
A
Tsukita
Sachiko
S
Tsukita
Shoichiro
S
Amagai
Masayuki
M
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D020224:Expressed Sequence Tags; D005187:Fallopian Tubes / Q000166:cytology*; D005260:Female; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology*; D014018:Tissue Distribution; D014132:Trachea / Q000033:anatomy & histology
D008869:Microtubule-Associated Proteins; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; C538999:sentan protein, mouse