title: Lengthening primary cilia enhances cellular mechanosensitivity.
abstract: The primary cilium is a mechanosensor in a variety of mammalian cell types, initiating and directing intracellular signalling cascades in response to external stimuli. When primary cilia formation is disrupted, cells have diminished mechanosensitivity and an abrogated response to mechanical stimulation. Due to this important role, we hypothesised that increasing primary cilia length would enhance the downstream response and therefore, mechanosensitivity. To test this hypothesis, we increased osteocyte primary cilia length with fenoldopam and lithium and found that cells with longer primary cilia were more mechanosensitive. Furthermore, fenoldopam treatment potentiated adenylyl cyclase activity and was able to recover primary cilia form and sensitivity in cells with impaired cilia. This work demonstrates that modulating the structure of the primary cilium directly impacts cellular mechanosensitivity. Our results implicate cilium length as a potential therapeutic target for combating numerous conditions characterised by impaired cilia function.
authors.forename: M
authors.initials: M
authors.lastname: Spasic
authors.affiliation: Columbia University, 351 Engineering Terr., 1210 Amsterdam Ave., Mail Code 8904, New York, NY, USA.crj2111@columbia.edu.
authors.forename: C R
authors.initials: CR
authors.lastname: Jacobs
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002923:Cilia / Q000187:drug effects / Q000378:metabolism*; D018818:Fenoldopam / Q000494:pharmacology; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D054852:Small Molecule Libraries; C490898:Tg737Rpw protein, mouse; D025521:Tumor Suppressor Proteins; D000262:Adenylyl Cyclases; D018818:Fenoldopam