Cell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis.

TitleCell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis.
Publication TypeJournal Article
Year of Publication2015
AuthorsWang, J, Kaletsky, R, Silva, M, Williams, A, Haas, LA, Androwski, RJ, Landis, JN, Patrick, C, Rashid, A, Santiago-Martinez, D, Gravato-Nobre, M, Hodgkin, J, Hall, DH, Murphy, CT, Barr, MM
JournalCurr Biol
Volume25
Issue24
Pagination3232-8
Date Published2015 Dec 21
ISSN1879-0445
KeywordsAnimals, Caenorhabditis elegans, Extracellular Vesicles, Female, Gene Expression Profiling, Male, Organelle Biogenesis, Sensory Receptor Cells, Sexual Behavior, Animal
Abstract

<p>Cilia and extracellular vesicles (EVs) are signaling organelles [1]. Cilia act as cellular sensory antennae, with defects resulting in human ciliopathies. Cilia both release and bind to EVs [1]. EVs are sub-micron-sized particles released by cells and function in both short- and long-range intercellular communication. In C. elegans and mammals, the autosomal dominant polycystic kidney disease (ADPKD) gene products polycystin-1 and polycystin-2 localize to both cilia and EVs, act in the same genetic pathway, and function in a sensory capacity, suggesting ancient conservation [2]. A fundamental understanding of EV biology and the relationship between the polycystins, cilia, and EVs is lacking. To define properties of a ciliated EV-releasing cell, we performed RNA-seq on 27 GFP-labeled EV-releasing neurons (EVNs) isolated from adult C. elegans. We identified 335 significantly overrepresented genes, of which 61 were validated by GFP reporters. The EVN transcriptional profile uncovered new pathways controlling EV biogenesis and polycystin signaling and also identified EV cargo, which included an antimicrobial peptide and ASIC channel. Tumor-necrosis-associated factor (TRAF) homologs trf-1 and trf-2 and the p38 mitogen-activated protein kinase (MAPK) pmk-1 acted in polycystin-signaling pathways controlling male mating behaviors. pmk-1 was also required for EV biogenesis, independent of the innate immunity MAPK signaling cascade. This first high-resolution transcriptome profile of a subtype of ciliated sensory neurons isolated from adult animals reveals the functional components of an EVN.</p>

DOI10.1016/j.cub.2015.10.057
Alternate JournalCurr. Biol.
PubMed ID26687621
PubMed Central IDPMC4698341
Grant ListDK059418 / DK / NIDDK NIH HHS / United States
DK074746 / DK / NIDDK NIH HHS / United States
OD 010943 / OD / NIH HHS / United States
R01 DK059418 / DK / NIDDK NIH HHS / United States
R01 DK074746 / DK / NIDDK NIH HHS / United States
R24 OD010943 / OD / NIH HHS / United States
R56 DK074746 / DK / NIDDK NIH HHS / United States
T32 HG003284 / HG / NHGRI NIH HHS / United States
/ / Medical Research Council / United Kingdom