title: Cell-Specific Transcriptional Profiling of Ciliated Sensory Neurons Reveals Regulators of Behavior and Extracellular Vesicle Biogenesis.
abstract: 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.
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Lewis Sigler Institute, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kaletsky
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Malan
authors.initials: M
authors.lastname: Silva
authors.affiliation: Department of Molecular Biology and Lewis Sigler Institute, Princeton University, Princeton, NJ 08544, USA.
authors.forename: April
authors.initials: A
authors.lastname: Williams
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Haas
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Androwski
authors.affiliation: Department of Molecular Biology and Lewis Sigler Institute, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Landis
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Patrick
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Alina
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Dianaliz
authors.initials: D
authors.lastname: Santiago-Martinez
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Gravato-Nobre
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hodgkin
authors.affiliation: Center for C. elegans Anatomy, Albert Einstein College of Medicine, 1410 Pelham Parkway, Bronx, NY 10461, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Hall
authors.affiliation: Department of Molecular Biology and Lewis Sigler Institute, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Coleen T
authors.initials: CT
authors.lastname: Murphy
authors.affiliation: Department of Genetics and Human Genetics Institute, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: barr@dls.rutgers.edu.
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Barr
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D000067128:Extracellular Vesicles / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D001678:Organelle Biogenesis; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012726:Sexual Behavior, Animal