Title: Lengthening primary cilia enhances cellular mechanosensitivity

Authors: M Spasic, CR Jacobs

Address: Department of Biomedical Engineering, Columbia University, New York, NY, USA

E-mail: crj2111 at columbia.edu

Key Words: Primary cilia, mechanosensitivity, fenoldopam, osteocyte.

Publication date: February 20th 2017

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.

Article download: Pages 158-168 (PDF file)
DOI: 10.22203/eCM.v033a12