Ectocytosis prevents accumulation of ciliary cargo in C. elegans sensory neurons.

Adria Razzauti,Patrick Laurent

doi:10.7554/elife.67670

Adria Razzauti, Patrick Laurent

Open Access

https://doi.org/10.7554/elife.67670

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Journal: eLife	Publication Date: Sep 17, 2021
Citations: 24	License type: CC BY 4.0

Affiliation: Université Libre de Bruxelles, Neuroscience Institute

Abstract

Cilia are sensory organelles protruding from cell surfaces. Release of extracellular vesicles (EVs) from cilia was previously observed in mammals, Chlamydomonas, and in male Caenorhabditis elegans. Using the EV marker TSP-6 (an ortholog of mammalian CD9) and other ciliary receptors, we show that EVs are formed from ciliated sensory neurons in C. elegans hermaphrodites. Release of EVs is observed from two ciliary locations: the cilia tip and/or periciliary membrane compartment (PCMC). Outward budding of EVs from the cilia tip leads to their release into the environment. EVs' budding from the PCMC is concomitantly phagocytosed by the associated glial cells. To maintain cilia composition, a tight regulation of cargo import and removal is achieved by the action of intra-flagellar transport (IFT). Unbalanced IFT due to cargo overexpression or mutations in the IFT machinery leads to local accumulation of ciliary proteins. Disposal of excess ciliary proteins via EVs reduces their local accumulation and exports them to the environment and/or to the glia associated to these ciliated neurons. We suggest that EV budding from cilia subcompartments acts as a safeguard mechanism to remove deleterious excess of ciliary material.

Highlights

Cilia are specialized sensory compartments protruding from the cell surfaces of many cell types, including sensory neurons
When TSP-7 was fused to mEGFP, the fusion proteins were still exported from AFD neurons to AMphid sheath (AMsh), TSP-7-mEGFP labelled Extracellular Vesicles (EVs) appeared less numerous and less bright than for TSP-7-wrmScarlet, suggesting both fusion proteins are partly located in acidic compartments after their export from AFD to AMsh (Figure 2 – figure supplement 2C). we show that TSP-6-wrmScarlet and TSP-7-wrmScarlet label ciliary membrane compartments
We showed that most of the ciliary membrane proteins we assessed are loaded into ciliary EVs which are readily taken up by AMsh

Summary

Introduction

Cilia are specialized sensory compartments protruding from the cell surfaces of many cell types, including sensory neurons. Sensory cilia of the olfactory and the photoreceptors neurons concentrate the signalling components required to sense and respond to chemicals or photons, respectively. Entry and retrieval of signalling components from cilia is mediated by large Intra-Flagellar Transport (IFT) trains moving membrane proteins bidirectionally along the ciliary microtubules. IFT operates together with cargo adapters such as the IFT-A and the BBSome complexes, respectively involved in entry and removal of transmembrane proteins from cilia. Sensory cilia integrity can be evaluated by sensory responses of the animals or by neuronal uptake of lipophilic dye (DiI) via its exposed ciliated ends [4, 5]. Mutations reducing cilia length cause dye filling defective phenotypes (Dyf) together with sensory defects [6]

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