Abstract
Background: 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.
Conclusion: 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.Keywords: Calcium signaling, InsP3 signaling, Apicomplexan parasites, Phosphoinositides, Plasmodium.
Current Topics in Medicinal Chemistry
Title:InsP3 Signaling in Apicomplexan Parasites
Volume: 17 Issue: 19
Author(s): Celia R.S. Garcia*, Eduardo Alves, Pedro H. S. Pereira, Paula J. Bartlett, Andrew P. Thomas, Katsuhiko Mikoshiba, Helmut Plattner and L. David Sibley
Affiliation:
- Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo. Sao Paulo 05508-090,Brazil
Keywords: Calcium signaling, InsP3 signaling, Apicomplexan parasites, Phosphoinositides, Plasmodium.
Abstract: Background: 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.
Conclusion: 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.Export Options
About this article
Cite this article as:
Garcia R.S. Celia*, Alves Eduardo, Pereira H. S. Pedro, Bartlett J. Paula, Thomas P. Andrew, Mikoshiba Katsuhiko, Plattner Helmut and Sibley David L., InsP3 Signaling in Apicomplexan Parasites, Current Topics in Medicinal Chemistry 2017; 17 (19) . https://dx.doi.org/10.2174/1568026617666170130121042
DOI https://dx.doi.org/10.2174/1568026617666170130121042 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Manipulation of Microglial Activation as a Therapeutic Strategy in Alzheimers Disease
Current Medicinal Chemistry Glutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders
CNS & Neurological Disorders - Drug Targets Brain-Derived Neurotrophic Factor and Antidepressant Activity
Current Pharmaceutical Design Targeting Neurotrophic Signal Transduction Pathways in the Treatment of Mood Disorders
Current Signal Transduction Therapy Metabotropic Glutamate Receptors in Central Nervous System Diseases
Current Drug Targets Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition
Current Medicinal Chemistry Association of Cerebrospinal Fluid Adiponectin Levels With Cerebral Glucose Metabolism In Mild Cognitive Impairment: A Pilot Study
Current Alzheimer Research Coenzyme Q10 in Neurodegenerative Diseases
Current Medicinal Chemistry Potential Mechanisms of Failure in the Sudden Infant Death Syndrome
Current Pediatric Reviews Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals
Current Pharmaceutical Design Targeting CSCs in Tumor Microenvironment: The Potential Role of ROS-Associated miRNAs in Tumor Aggressiveness
Current Stem Cell Research & Therapy Physiology, Pharmacology and Pathophysiology of the pH Regulatory Transport Proteins NHE1 and NBCn1: Similarities, Differences, and Implications for Cancer Therapy
Current Pharmaceutical Design Beyond the Direct Activation of Cannabinoid Receptors: New Strategies to Modulate the Endocannabinoid System in CNS-Related Diseases
Recent Patents on CNS Drug Discovery (Discontinued) New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is)
Current Medicinal Chemistry Significance of Pharmacogenetics and Pharmacogenomics Research in Current Medical Practice
Current Drug Metabolism Multigate Quality Doppler Profiles and Morphological/Hemodynamic Alterations in Multiple Sclerosis Patients
Current Neurovascular Research Protein Kinases and Associated Pathways in Pluripotent State and Lineage Differentiation
Current Stem Cell Research & Therapy Biosafety of Recombinant Adeno-associated Virus Vectors
Current Gene Therapy Substance P and Alzheimer’s Disease: Emerging Novel Roles
Current Alzheimer Research Pharmacological Characteristics of Parenteral IGF-I Administration
Current Pharmaceutical Biotechnology