Primary cilia: Cell and molecular mechanosensors directing whole tissue function

Abstract

Primary cilia are immotile, microtubule-based organelles extending from the surface of nearly every mammalian cell. Mechanical stimulation causes deflection of the primary cilium, initiating downstream signaling cascades to the rest of the cell. The cilium forms a unique subcellular microdomain, and defects in ciliary protein composition or physical structure have been associated with a myriad of human pathologies. In this review, we discuss the importance of ciliary mechanotransduction at the cell and tissue level, and how furthering our molecular understanding of primary cilia mechanobiology may lead to therapeutic strategies to treat human diseases.

Keywords: Ciliopathy; Mechanosensor; Mechanotransduction; Microdomain; Primary cilia.

Figure 1

Pharmacologic intervention can increase primary cilia length. Osteocytes treated with fenoldopam (right) have elongated cilia compared to control (left). Cilia were stained with antibody against acetylated α-tubulin from a C3B9 hybridoma cell line, and visualized with Alexa Fluor 488 secondary antibody. Nuclei were stained with DAPI. Scale bar represents 20 μm.

Figure 2

The primary cilia mechanosensing apparatus may utilize distinct pathways in different cell types to initiate signaling cascades. One potential example is TRPV4 mediating primary cilia mechanosensing in osteocytes, while PC2 is dominant in kidney epithelial cells. Further proteomic and biosensor studies will discern cell-specific differences in cilia proteomes, enabling therapeutic interventions targeted at primary cilia of distinct cell types.