EV duty vehicles: Features and functions of ciliary extracellular vesicles

Abstract

The primary cilium is a microtubule-based organelle that extends from a basal body at the surface of most cells. This antenna is an efficient sensor of the cell micro-environment and is instrumental to the proper development and homeostatic control of organs. Recent compelling studies indicate that, in addition to its role as a sensor, the primary cilium also emits signals through the release of bioactive extracellular vesicles (EVs). While some primary-cilium derived EVs are released through an actin-dependent ectocytosis and are called ectosomes (or large EVs, 350–500 nm), others originate from the exocytosis of multivesicular bodies and are smaller (small EVs, 50–100 nm). Ciliary EVs carry unique signaling factors, including protein markers and microRNAs (miRNAs), and participate in intercellular communication in different organism models. This review discusses the mechanism of release, the molecular features, and functions of EVs deriving from cilia, based on the existing literature.

Extracellular vesicle-mediated delivery of anti-miR-106b inhibits morphine-induced primary ciliogenesis in the brain

“…Ciliary EVs can be generated at the ciliary tip, the axoneme, and the ciliary base. 88 It is worth exploring the possibility that morphine-triggered EV release could be due to the promotion of primary ciliogenesis by morphine in future investigations.…”

Emerging principles of primary cilia dynamics in controlling tissue organization and function

“…This could also be viewed as a safety valve mechanism to prevent protein overload or excessive ciliary elongation, which has been observed in a multitude of different organisms (Nager et al , 2017 ; Akella et al , 2020 ; Razzauti & Laurent, 2021 ). EV biogenesis also controls cilia length (Long et al , 2016 ; Phua et al , 2017 ), and modulates ciliation via initiating cell cycle re‐entry into mitosis (Phua et al , 2017 ; Wang et al , 2019 ), as covered by other recent reviews (Wang & Barr, 2018 ; Ikegami & Ijaz, 2021 ; Ojeda Naharros & Nachury, 2022 ; Vinay & Belleannee, 2022 ). Since EVs are important in intercellular communication in many tissues, it is tempting to speculate that the dynamic generation and shedding of ciliary EVs control tissue organization and function.…”

“…Recent studies revealed that cilia not only function as signal receivers but are also able to transmit signals by releasing bioactive extracellular vesicles (EVs) containing proteins and mRNAs (Wang & Barr, 2018 ; Luxmi & King, 2022 ; Ojeda Naharros & Nachury, 2022 ; Vinay & Belleannee, 2022 ). This has mainly been studied in Chlamydomonas (Wood et al , 2013 ) or in C. elegans (Wang et al , 2015 , 2021 ; Wang & Barr, 2018 ), where ciliary EVs are involved in mating and behavior.…”

Cilia Provide a Platform for the Generation, Regulated Secretion, and Reception of Peptidergic Signals

“…These can form at the ciliary tip or along the entire length of the cilium (reviewed in [58]). The membrane topology of ectosome budding is such that proteins on the external face of the ciliary membrane will appear on the outer surface of the ectosomes contacting the environment, while their luminal contents are derived from the cilioplasm (i.e., the non-axonemal components inside the ciliary membrane).…”