Differentiated dynamic response in C. elegans chemosensory cilia

Abstract

SummaryCilia are membrane-enveloped organelles that protrude from the surface of most eurokaryotic cells and play crucial roles in sensing the external environment. For maintenance and function cilia are dependent on intraflagellar transport (IFT). Here we use a combination of microfluidics and fluorescence microscopy to study the response of phasmid chemosensory neurons, in live Caenorhabditis elegans, to chemical stimuli. We found that chemical stimulation resulted in unexpected changes in IFT and ciliary structure. Notably, stimulation with hyperosmotic solutions or chemical repellents resulted in different responses, not only in IFT, ciliary structure and cargo distribution, but also in neuronal activity. The response to chemical repellents results in habituation of the neuronal activity, suggesting that IFT plays a role in regulating the chemosensory response. Our findings show that cilia are able to sense and respond to different external cues in distinct ways, highlighting the flexible nature of cilia as sensing hubs.

Mechanisms of Regulation in Intraflagellar Transport

“…A study employing dendritic laser ablation to block the supply of new material into cilia showed that IFT components redistribute after ablation to the base, followed by shortening of the axoneme [ 149 ]. More recently, similar behavior was observed in response to the chemical repellents the chemosensory cilia sense [ 32 ]. In these experiments, MTs shortened, disappearing from the distal segment in a reversible fashion, (reversibly) decreasing the ability of the cilium to react to subsequent stimuli.…”

“…A big open question is, however, how IFT dynein switches from the autoinhibited to an active state during anterograde-to-retrograde conversion of trains at the ciliary tip. Furthermore, while we know that IFT-dynein activity is tightly regulated, it is not clear what the regulatory players are that drive rapid redistribution of IFT dynein and other IFT components after external stimuli [ 32 ].…”

“…Studies where the activity or interaction kinetics of proteins can be dynamically switched on and off, for example by optogenetics [ 205 , 206 ], chemical means [ 89 ], or auxin-inducible degron system [ 207 , 208 ], would significantly improve our understanding of the functional role of IFT proteins. Furthermore, recently it was found in C. elegans primary cilia that the steady state of IFT regulation can be promptly and substantially altered by providing external stimuli [ 32 ]. It is not clear yet whether such dynamic IFT-regulation mechanisms are also active in cilia of other species.…”

“…Recently, it has been shown that in C. elegans chemosensory cilia, IFT is affected by chemical stimulation. Chemical stimulation not only results in neuronal signaling, but also causes a considerable redistribution of IFT components over the cilium [ 32 ]. These observations show that IFT is indeed under tight control, and that this control is used by the cilia to adapt to different conditions.…”