C. elegans Ciliated Sensory Neurons Release Extracellular Vesicles that Function in Animal Communication

Abstract

Summary Cells release extracellular vesicles (ECVs) that play important roles in intercellular communication and may mediate a broad range of physiological and pathological processes. Many fundamental aspects of ECV biogenesis and signaling have yet to be determined, with ECV detection being a challenge and obstacle due to their small size (100nm). We developed an in vivo system to visualize the dynamic release of GFP-labeled ECVs. We show here that specific Caenorhabdidits elegans ciliated sensory neurons shed and release ECVs containing GFP-tagged polycystins LOV-1 and PKD-2. These ECVs are also abundant in the lumen surrounding the cilium. Electron tomography and genetic analysis indicate that ECV biogenesis occurs via budding from the plasma membrane at the ciliary base and not via fusion of multivesicular bodies (MVBs). Intraflagellar transport (IFT) and kinesin-3 KLP-6 are required for environmental release of PKD-2::GFP-containing ECVs. ECVs isolated from wild-type animals induce male tail chasing behavior, while ECVs isolated from klp-6 animals and lacking PKD-2::GFP do not. We conclude that environmentally released ECVs play a role in animal communication and mating related behaviors.

Beta cell connectivity in pancreatic islets: a type 2 diabetes target?

“…While studies of Kif3a, Lkb1, and Rfx3 knockout mice have all invoked a role for cilia in pancreatic development (i.e., ductal and endocrine cell specification) [87,[89][90][91], little is known about their involvement in cell-cell signaling processes within the islet. Given the role of cilia in signal transmission in in other tissues [92], and potentially in exosome-mediated intercellular communications [93], we believe this warrants further investigation. Paracrine signaling Intercellular communication may also be possible via the production and secretion of messengers which act on neighboring cells [20,21,28].…”

Model Organisms in G Protein–Coupled Receptor Research

“…PC1 proteins, like aGPCRs, contain a GPCR autoproteolysis-inducing domain, undergo autoproteolytic cleavage at a GPS into N-terminal and C-terminal regions, and can activate G protein second messengers, endowing them with GPCR-like properties (Delmas et al, 2004;Yu et al, 2007;Prömel et al, 2013). LOV-1 possesses a GPS, and an N-terminal region lacking TM domains remains associated with cilia and extracellular vesicles, suggesting that LOV-1 may be an atypical aGPCR (Barr and Sternberg, 1999;O'Hagan et al, 2014;Wang et al, 2014).…”

“…has been using C. elegans as a model for studying mechanisms regulating the localization and functions of the polycystins in cilia and extracellular vesicles (O'Hagan et al, 2014;Wang et al, 2014). PC1 proteins, like aGPCRs, contain a GPCR autoproteolysis-inducing domain, undergo autoproteolytic cleavage at a GPS into N-terminal and C-terminal regions, and can activate G protein second messengers, endowing them with GPCR-like properties (Delmas et al, 2004;Yu et al, 2007;Prömel et al, 2013).…”

Identification of Biomarkers for PKD1 Using Urinary Exosomes

“…This suggests that ELVs represent a phylogenetically ancient signaling mechanism and that the study of human urinary ELVs will shed light on the pathophysiologic mechanisms underlying ADPKD. 10 …”