title: InsP3 Signaling in Apicomplexan Parasites.
abstract: Phosphoinositides (PIs) and their derivatives are essential cellular components that form the building blocks for cell membranes and regulate numerous cell functions. Specifically, the ability to generate myo-inositol 1,4,5-trisphosphate (InsP3) via phospholipase C (PLC) dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to InsP3 and diacylglycerol (DAG) initiates intracellular calcium signaling events representing a fundamental signaling mechanism dependent on PIs. InsP3 produced by PI turnover as a second messenger causes intracellular calcium release, especially from endoplasmic reticulum, by binding to the InsP3 receptor (InsP3R). Various PIs and the enzymes, such as phosphatidylinositol synthase and phosphatidylinositol 4-kinase, necessary for their turnover have been characterized in Apicomplexa, a large phylum of mostly commensal organisms that also includes several clinically relevant parasites. However, InsP3Rs have not been identified in genomes of apicomplexans, despite evidence that these parasites produce InsP3 that mediates intracellular Ca2+ signaling.
  
  
  
  Evidence to supporting IP3-dependent signaling cascades in apicomplexans suggests that they may harbor a primitive or non-canonical InsP3R. Understanding these pathways may be informative about early branching eukaryotes, where such signaling pathways also diverge from animal systems, thus identifying potential novel and essential targets for therapeutic intervention.
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo. Sao Paulo 05508-090, Brazil
authors.forename: Celia R S
authors.initials: CRS
authors.lastname: Garcia
authors.affiliation: Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo. Sao Paulo 05508-000, Brazil
authors.forename: Eduardo
authors.initials: E
authors.lastname: Alves
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo. Sao Paulo 05508-090, Brazil|Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo. Sao Paulo 05508-000, Brazil
authors.forename: Pedro H S
authors.initials: PHS
authors.lastname: Pereira
authors.affiliation: New Jersey Medical School, Rutgers, The State University of New Jersey, New Jersey, USA
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Bartlett
authors.affiliation: New Jersey Medical School, Rutgers, The State University of New Jersey, New Jersey, USA
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Thomas
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama, Japan
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.affiliation: Department of Biology, University of Konstanz, 78457 Konstanz, Germany
authors.forename: Helmut
authors.initials: H
authors.lastname: Plattner
authors.affiliation: Department of Molecular Microbiology, Washington University Sch. Med., Saint Louis, USA
authors.forename: L David
authors.initials: LD
authors.lastname: Sibley
mesh_terms: D000818:Animals; D016782:Apicomplexa / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction
chemical_list: D015544:Inositol 1,4,5-Trisphosphate
keywords: Apicomplexan parasites; Calcium signaling; InsP3 signaling; Phosphoinositides; Plasmodium