Abstract
Lysosomal enzymes undergo phosphorylation on their mannose residues in the Golgi apparatus and are recognized by two distinct type I transmembrane glycoproteins designated as the mannose 6-phosphate receptors; MPR300, (Mr 300 kDa) and MPR46, (Mr 46 kDa) that internally transport them to the lysosomes. In humans, absence of this recognition system leads to severe lysosomal storage disease, emphasizing their essential role in the biogenesis of lysosomes. Among the two receptors only MPR46 shows an absolute requirement for divalent metal ions. Only MPR300 is known to be a multifunctional protein that also binds many other ligands such as the human IGF-II, thyroglobulin, retinoic acid, granzyme A and B. In mammals, the extracytoplasmic domain of MPR300 protein is comprised of 15 repetitive cassettes which share significant similarity with each other and also with the single cassette that constitutes the extracytoplasmic domain of MPR46. Therefore it became necessary to understand the evolution of these receptors. Homologous proteins were affinity purified from different non-mammalian vertebrates such as birds, reptiles, amphibians, fish and also from the invertebrates, echinodermates (starfish) and molluscs (unio). Cloning and sequencing of both receptors from different mammals, chicken, fish and MPR46 from starfish revealed that these proteins exhibit similar structural domains as the mammalian receptors. α-fucosidase characterized from the molluscs exhibits specific interaction with the putative MPR300 protein from the same species. Available evidence suggests evolutionary conservation of both receptors from molluscs, as below these species no receptors that bind phosphomannan have been identified.
Keywords: Mannose 6-phosphate, phosphomannan-Sepharose, affinity chromatography, evolution, vertebrates, nonmammalian vertebrates, invertebrates, MPR300, MPR46
Current Protein & Peptide Science
Title: Evolution of Mannose 6-Phosphate Receptors (MPR300 and 46): Lysosomal Enzyme Sorting Proteins
Volume: 11 Issue: 1
Author(s): S. K. Nadimpalli and P. K. Amancha
Affiliation:
Keywords: Mannose 6-phosphate, phosphomannan-Sepharose, affinity chromatography, evolution, vertebrates, nonmammalian vertebrates, invertebrates, MPR300, MPR46
Abstract: Lysosomal enzymes undergo phosphorylation on their mannose residues in the Golgi apparatus and are recognized by two distinct type I transmembrane glycoproteins designated as the mannose 6-phosphate receptors; MPR300, (Mr 300 kDa) and MPR46, (Mr 46 kDa) that internally transport them to the lysosomes. In humans, absence of this recognition system leads to severe lysosomal storage disease, emphasizing their essential role in the biogenesis of lysosomes. Among the two receptors only MPR46 shows an absolute requirement for divalent metal ions. Only MPR300 is known to be a multifunctional protein that also binds many other ligands such as the human IGF-II, thyroglobulin, retinoic acid, granzyme A and B. In mammals, the extracytoplasmic domain of MPR300 protein is comprised of 15 repetitive cassettes which share significant similarity with each other and also with the single cassette that constitutes the extracytoplasmic domain of MPR46. Therefore it became necessary to understand the evolution of these receptors. Homologous proteins were affinity purified from different non-mammalian vertebrates such as birds, reptiles, amphibians, fish and also from the invertebrates, echinodermates (starfish) and molluscs (unio). Cloning and sequencing of both receptors from different mammals, chicken, fish and MPR46 from starfish revealed that these proteins exhibit similar structural domains as the mammalian receptors. α-fucosidase characterized from the molluscs exhibits specific interaction with the putative MPR300 protein from the same species. Available evidence suggests evolutionary conservation of both receptors from molluscs, as below these species no receptors that bind phosphomannan have been identified.
Export Options
About this article
Cite this article as:
Nadimpalli K. S. and Amancha K. P., Evolution of Mannose 6-Phosphate Receptors (MPR300 and 46): Lysosomal Enzyme Sorting Proteins, Current Protein & Peptide Science 2010; 11 (1) . https://dx.doi.org/10.2174/138920310790274644
DOI https://dx.doi.org/10.2174/138920310790274644 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Can we Consider Zoledronic Acid a New Antitumor Agent? Recent Evidence in Clinical Setting
Current Cancer Drug Targets MiRNA153 Reduces Effects of Chemotherapeutic Agents or Small Molecular Kinase Inhibitor in HCC Cells
Current Cancer Drug Targets Signal Transducer and Activator of Transcription 3 Signaling Pathway: A Potential Target in Sarcoma Treatment
Current Enzyme Inhibition Inorganic Phosphate as a Signaling Molecule: A Potential Strategy in Osteosarcoma Treatment
Current Pharmaceutical Design Berberine Exerts Anti-cancer Activity by Modulating Adenosine Monophosphate- Activated Protein Kinase (AMPK) and the Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) Signaling Pathways
Current Pharmaceutical Design CSPG4 in Cancer: Multiple Roles
Current Molecular Medicine Ewing Sarcoma Family Tumors: Past, Present and Future Prospects
Current Cancer Therapy Reviews Cyclopamine, a Naturally Occurring Alkaloid, and Its Analogues May Find Wide Applications in Cancer Therapy
Current Topics in Medicinal Chemistry Regulatory Mechanisms of Chondrogenesis and Implications for Understanding Articular Cartilage Homeostasis
Current Rheumatology Reviews Tumor-Targeting Peptides and Small Molecules as Anti-Cancer Agents to Overcome Drug Resistance
Current Medicinal Chemistry Current Management of Chordoma
Current Drug Therapy The Role of miR-129-5p in Cancer: A Novel Therapeutic Target
Current Molecular Pharmacology Brain Tumor Causes, Symptoms, Diagnosis and Radiotherapy Treatment
Current Medical Imaging The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors
Mini-Reviews in Medicinal Chemistry The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Recent Patents on Anti-Cancer Drug Discovery The Roles of Endoplasmic Reticulum Stress in the Pathophysiological Development of Cartilage and Chondrocytes
Current Pharmaceutical Design New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Tumor Stroma Manipulation By MSC
Current Drug Targets Serpins for Diagnosis and Therapy in Cancer
Cardiovascular & Hematological Disorders-Drug Targets Multicolor-FISH Approaches for the Characterization of Human Chromosomes in Clinical Genetics and Tumor Cytogenetics
Current Genomics