Wang J et al. (2016) Cell Mol Neurobiol "Ciliary Extracellular Vesicles: Txt Msg Organelles."

Barr MM, Wang J

[Cell Mol Neurobiol, 2016]

Cilia are sensory organelles that protrude from cell surfaces to monitor the surrounding environment. In addition to its role as sensory receiver, the cilium also releases extracellular vesicles (EVs). The release of sub-micron sized EVs is a conserved form of intercellular communication used by all three kingdoms of life. These extracellular organelles play important roles in both short and long range signaling between donor and target cells and may coordinate systemic responses within an organism in normal and diseased states. EV shedding from ciliated cells and EV-cilia interactions are evolutionarily conserved phenomena, yet remarkably little is known about the relationship between the cilia and EVs and the fundamental biology of EVs. Studies in the model organisms Chlamydomonas and Caenorhabditis elegans have begun to shed light on ciliary EVs. Chlamydomonas EVs are shed from tips of flagella and are bioactive. Caenorhabditis elegans EVs are shed and released by ciliated sensory neurons in an intraflagellar transport-dependent manner. Caenorhabditis elegans EVs play a role in modulating animal-to-animal communication, and this EV bioactivity is dependent on EV cargo content. Some ciliary pathologies, or ciliopathies, are associated with abnormal EV shedding or with abnormal cilia-EV interactions. Until the 21st century, both cilia and EVs were ignored as vestigial or cellular junk. As research interest in these two organelles continues to gain momentum, we envision a new field of cell biology emerging. Here, we propose that the cilium is a dedicated organelle for EV biogenesis and EV reception. We will also discuss possible mechanisms by which EVs exert bioactivity and explain how what is learned in model organisms regarding EV biogenesis and function may provide insight to human ciliopathies.

Wang J et al. (2024) Genetics "Extracellular vesicles."

Barr MM, Wehman AM, Wang J

[Genetics, 2024]

Extracellular vesicles (EVs) encompass a diverse array of membrane-bound organelles released outside cells in response to developmental and physiological cell needs. EVs play important roles in remodeling the shape and content of differentiating cells and can rescue damaged cells from toxic or dysfunctional content. EVs can send signals and transfer metabolites between tissues and organisms to regulate development, respond to stress or tissue damage, or alter mating behaviors. While many EV functions have been uncovered by characterizing ex vivo EVs isolated from body fluids and cultured cells, research using the nematode Caenorhabditis elegans has provided insights into the in vivo functions, biogenesis, and uptake pathways. The C. elegans EV field has also developed methods to analyze endogenous EVs within the organismal context of development and adult physiology in free-living, behaving animals. In this review, we summarize major themes that have emerged for C. elegans EVs and their relevance to human health and disease. We also highlight the diversity of biogenesis mechanisms, locations, and functions of worm EVs and discuss open questions and unexplored topics tenable in C. elegans, given the nematode model is ideal for light and electron microscopy, genetic screens, genome engineering, and high-throughput omics.

Akella JS et al. (2020) Dev Neurobiol "The tubulin code specializes neuronal cilia for extracellular vesicle release."

Barr MM, Akella JS

[Dev Neurobiol, 2020]

Cilia are microtubule-based organelles that display diversity in morphology, ultrastructure, protein composition, and function. The ciliary microtubules of C. elegans sensory neurons exemplify this diversity and provide a paradigm to understand mechanisms driving ciliary specialization. Only a subset of ciliated neurons in C. elegans are specialized to make and release bioactive extracellular vesicles (EVs) into the environment. The cilia of extracellular vesicle releasing neurons have distinct axonemal features and specialized intraflagellar transport that are important for releasing EVs. In this review, we discuss the role of the tubulin code in the specialization of microtubules in cilia of EV releasing neurons.

Wang J et al. (2018) Essays Biochem "Cell-cell communication via ciliary extracellular vesicles: clues from model systems."

Barr MM, Wang J

[Essays Biochem, 2018]

In this short review, we will focus on the uniqueness of ciliary extracellular vesicles (EVs). In particular, we will review what has been learned regarding EVs produced by cilia of model organisms. Model systems including <i>Chlamydomonas, Caenorhabditis elegans</i>, and mouse revealed the fundamental biology of cilia and flagella and provide a paradigm to understand the roles of cilia and flagella in human development, health, and disease. Likewise, we propose that general principles learned from model systems regarding ciliary EV biogenesis and functions may provide a framework to explore the roles of ciliary EVs in human development, health, and disease.