title: The Lipocalin LPR-1 Cooperates with LIN-3/EGF Signaling To Maintain Narrow Tube Integrity inCaenorhabditis elegans.
abstract: Lipocalins are secreted cup-shaped glycoproteins that bind sterols, fatty acids, and other lipophilic molecules. Lipocalins have been implicated in a wide array of processes related to lipophilic cargo transport, sequestration, and signaling, and several are used as biomarkers for human disease, but the functions of most lipocalins remain poorly understood. Here we show that theCaenorhabditis eleganslipocalin LPR-1 is required to maintain apical membrane integrity and a continuous lumen in two narrow unicellular tubes, the excretory duct and pore, during a period of rapid lumen elongation. LPR-1 fusion protein is expressed by the duct and pore and accumulates both intracellularly and in apical extracellular compartments, but it can also function cell nonautonomously when provided from outside of the excretory system.lpr-1mutant defects can be rescued by increased signaling through the epidermal growth factor (EGF)-Ras-extracellular signal regulated kinase (ERK) pathway, which promotes the more elongated ductvs.less elongated pore tube fate. Spatial and temporal rescue experiments indicate that Ras signaling acts within the duct and pore tubes during or prior to cell fate determination to bypass the requirement for LPR-1lpr-1mutations did not disrupt LIN-3/EGF-dependent duct-fate specification, prevent functioning of any specific LIN-3/EGF isoform, or alter LET-23/EGFR localization, and reduced signaling did not phenocopy or enhancelpr-1mutant defects. These data suggest that LPR-1 protects lumen integrity through a LIN-3/EGF-independent mechanism, but that increased signaling upregulates some target(s) that can compensate forlpr-1absence.
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Pu
authors.initials: P
authors.lastname: Pu
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Stone
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Burdick
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: John I
authors.initials: JI
authors.lastname: Murray
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 sundaram@mail.med.upenn.edu.
authors.forename: Meera V
authors.identifier: 0000-0002-2940-8750
authors.initials: MV
authors.lastname: Sundaram
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004703:Endocrine System / Q000254:growth & development / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D054834:Lipocalins; C075912:Lin-3 protein, C elegans; D004815:Epidermal Growth Factor; D018631:ras Proteins
keywords: Caenorhabditis elegans; excretory system; lipocalin; signaling; tubulogenesis