title: Neuronal serotonin release triggers the heat shock response in C. elegans in the absence of temperature increase.
abstract: BACKGROUND
  Cellular mechanisms aimed at repairing protein damage and maintaining homeostasis, widely understood to be triggered by the damage itself, have recently been shown to be under cell nonautonomous control in the metazoan C. elegans. The heat shock response (HSR) is one such conserved mechanism, activated by cells upon exposure to proteotoxic conditions such as heat. Previously, we had shown that this conserved cytoprotective response is regulated by the thermosensory neuronal circuitry of C. elegans. Here, we investigate the mechanisms and physiological relevance of neuronal control.
  
  
  RESULTS
  By combining optogenetic methods with live visualization of the dynamics of the heat shock transcription factor (HSF1), we show that excitation of the AFD thermosensory neurons is sufficient to activate HSF1 in another cell, even in the absence of temperature increase. Excitation of the AFD thermosensory neurons enhances serotonin release. Serotonin release elicited by direct optogenetic stimulation of serotonergic neurons activates HSF1 and upregulates molecular chaperones through the metabotropic serotonin receptor SER-1. Consequently, excitation of serotonergic neurons alone can suppress protein misfolding in C. elegans peripheral tissue.
  
  
  CONCLUSIONS
  These studies imply that thermosensory activity coupled to serotonergic signaling is sufficient to activate the protective HSR prior to frank proteotoxic damage. The ability of neurosensory release of serotonin to control cellular stress responses and activate HSF1 has powerful implications for the treatment of protein conformation diseases.
authors.affiliation: Department of Biology, Aging Mind and Brain Initiative, University of Iowa, 338 Biology Building East, 210 Iowa Avenue, Iowa City, IA 52242-1324, USA.
authors.forename: Marcus C
authors.initials: MC
authors.lastname: Tatum
authors.affiliation: Department of Biology, Aging Mind and Brain Initiative, University of Iowa, 338 Biology Building East, 210 Iowa Avenue, Iowa City, IA 52242-1324, USA.
authors.forename: Felicia K
authors.initials: FK
authors.lastname: Ooi
authors.affiliation: Department of Biology, Aging Mind and Brain Initiative, University of Iowa, 338 Biology Building East, 210 Iowa Avenue, Iowa City, IA 52242-1324, USA.
authors.forename: Madhusudana Rao
authors.initials: MR
authors.lastname: Chikka
authors.affiliation: Department of Molecular Biosciences, Rice Institute for Biomedical Sciences, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208-3500, USA.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Chauve
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208002, New Haven, CT 06520-8002, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Martinez-Velazquez
authors.affiliation: Department Translational Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Center, Universiteitssingel 40, Room 2.578, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
authors.forename: Harry W M
authors.initials: HWM
authors.lastname: Steinbusch
authors.affiliation: Department of Molecular Biosciences, Rice Institute for Biomedical Sciences, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208-3500, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Morimoto
authors.affiliation: Department of Biology, Aging Mind and Brain Initiative, University of Iowa, 338 Biology Building East, 210 Iowa Avenue, Iowa City, IA 52242-1324, USA. Electronic address: veena-prahlad@uiowa.edu.
authors.forename: Veena
authors.initials: V
authors.lastname: Prahlad
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018869:Heat-Shock Response; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; C474710:heat shock factor-1, C elegans; D012701:Serotonin