Intracellular and extracellular forces drive primary cilia movement

Abstract

Primary cilia are ubiquitous, microtubule-based organelles that play diverse roles in sensory transduction in many eukaryotic cells. They interrogate the cellular environment through chemosensing, osmosensing, and mechanosensing using receptors and ion channels in the ciliary membrane. Little is known about the mechanical and structural properties of the cilium and how these properties contribute to ciliary perception. We probed the mechanical responses of primary cilia from kidney epithelial cells [Madin-Darby canine kidney-II (MDCK-II)], which sense fluid flow in renal ducts. We found that, on manipulation with an optical trap, cilia deflect by bending along their length and pivoting around an effective hinge located below the basal body. The calculated bending rigidity indicates weak microtubule doublet coupling. Primary cilia of MDCK cells lack interdoublet dynein motors. Nevertheless, we found that the organelles display active motility. 3D tracking showed correlated fluctuations of the cilium and basal body. These angular movements seemed random but were dependent on ATP and cytoplasmic myosin-II in the cell cortex. We conclude that force generation by the actin cytoskeleton surrounding the basal body results in active ciliary movement. We speculate that actin-driven ciliary movement might tune and calibrate ciliary sensory functions.

Early development of the nervous system of the eutherian <i>Tupaia belangeri</i>

“…© Springer-Verlag 1999, with kind permission from Springer Science and Business Media. tween macrophages and apoptotic cells could be demonstrated in the catshark (Bejarano-Escobar et al, 2013). For these and other reasons, Francisco-Morcillo et al (2014) conclude that, in the developing visual system, "dying cells show similar but not identical spatiotemporally restricted patterns in different vertebrates".…”

“…However, it is still unclear how this type of planar polarity is established in cones and what its functional impacts are. This may be about to change in view of the exciting new discovery that, in kidney epithelial cells, primary cilia (9 + 0 cilia) undergo active fluctuations in the absence of dyneins (Battle et al, 2015). small supranuclear mitochondria are attached to cytoplasmic microtubules (MT).…”

YAP and TAZ: a nexus for Hippo signaling and beyond

“…The Hippo pathway both controls and is regulated by the primary cilia [94,153–155], a microtubule-based solitary sensory signaling organelle comprising a special part of the plasma membrane in most eukaryotic quiescent cells [156]. The primary cilia respond to mechanical signals [157] and dynamically localize and regulate a range of receptors mediated by YAP/TAZ, such as GPCRs, sonic hedgehog (shh), the TGFβ family, receptor tyrosine kinases, and Wnt receptors [7,10,14,17,22,23,158]. This regulation of receptors is predominantly mediated through the cilia transition zone, the cellular gatekeeper for receptors destined for cilial localization [156].…”

Primary cilia: Cell and molecular mechanosensors directing whole tissue function

“…For example, primary cilia are distinct from motile cilia which contain actin filaments to drive motion, and it was believed that primary cilia lacked this actin connectivity. However, APEX labeling uncovered that actin and actin-binding proteins are actually trafficked to the primary cilium as well, potentially supporting the hypothesis that actin forces tune cilia mechanosensing [73]. …”

“…It has been suggested that the actin cytoskeleton surrounding the basal body of the cilium may also generate force to adjust ciliary positioning to tune and calibrate sensory functions [73]. In fact, treatment with the actin destabilizer, cytochalasin D, induces ciliogenesis, though it has not been clearly defined how this impacts primary cilia-medaited mechanotransduction [74].…”