Advertisement

Topics

Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect.

Summary of "Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect."

Neuromuscular junctions (NMJs) are synapses that transmit impulses from motor neurons to skeletal muscle fibers leading to muscle contraction. Study of hereditary disorders of neuromuscular transmission, termed congenital myasthenic syndromes (CMS), has helped elucidate fundamental processes influencing development and function of the nerve-muscle synapse. Using genetic linkage, we find 18 different biallelic mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in 13 unrelated families with an autosomal recessive CMS. Consistent with these data, downregulation of the GFPT1 ortholog gfpt1 in zebrafish embryos altered muscle fiber morphology and impaired neuromuscular junction development. GFPT1 is the key enzyme of the hexosamine pathway yielding the amino sugar UDP-N-acetylglucosamine, an essential substrate for protein glycosylation. Our findings provide further impetus to study the glycobiology of NMJ and synapses in general.

Affiliation

Institute of Cell Biology, Eidgenössische Technische Hochschule (ETH) Zürich, 8093 Zürich, Switzerland; Institute of Human Genetics, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, 52074 Aachen, Germany.

Journal Details

This article was published in the following journal.

Name: American journal of human genetics
ISSN: 1537-6605
Pages: 162-72

Links

DeepDyve research library

PubMed Articles [12727 Associated PubMed Articles listed on BioPortfolio]

Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1).

Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first enzyme of the hexosamine biosynthetic pathway. It transfers an amino group from glutamine to fructose-6-phosphate to yield glucosamin...

Epithelial mesenchymal transition induces aberrant glycosylation through hexosamine biosynthetic pathway activation.

Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been focuse...

Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome.

To describe the clinical and electrophysiologic features of synaptotagmin II (SYT2) mutations, a novel neuromuscular syndrome characterized by foot deformities and fatigable ocular and lower limb weak...

The Plasma Membrane Protein Nce102 Implicated in Eisosome Formation Rescues A Heme Defect in Mitochondria.

The cellular transport of the cofactor heme, and its biosynthetic intermediates such as protoporphyrin IX, is a complex and highly coordinated process. To investigate the molecular details of this tra...

Elucidation of Pyranonigrin Biosynthetic Pathway Reveals a Mode of Tetramic Acid, Fused γ-Pyrone, and exo-Methylene Formation.

Successful activation of the pyranonigrin biosynthetic gene cluster and gene knockout in Aspergillus niger plus in vivo and in vitro assays led to isolation of six new products, including a spiro cycl...

Clinical Trials [1649 Associated Clinical Trials listed on BioPortfolio]

Neuromuscular Transmission in Amyotrophic Lateral Sclerosis

Consistent data suggest that neuromuscular transmission is impaired in ALS patients. Neuromuscular junctions dysfunction may appear very early in the disease, as shown by data in animal mo...

Studies in Porphyria I: Characterization of Enzyme Defects

OBJECTIVES: I. Characterize enzyme defects in patients with known or suspected porphyria and their family members. II. Determine whether selected patients are eligible for other porphyr...

The Neuromuscular Effect of Rocuronium in Patient

Rocuronium block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. There have been several studies reported positive relationshi...

Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

The goal of this study is to establish a genetic registry of patients with early-onset motor neuron and neuromuscular diseases. The investigators will collect samples from patients with a ...

Genetics of Cardiovascular and Neuromuscular Disease

We are studying the genetics of human cardiovascular and neuromuscular disease. There are many different genetic regions that have been associated with the development of cardiomyopathy. ...

Medical and Biotech [MESH] Definitions

A heterogeneous group of disorders characterized by a congenital defect in neuromuscular transmission at the NEUROMUSCULAR JUNCTION. This includes presynaptic, synaptic, and postsynaptic disorders (that are not of autoimmune origin). The majority of these diseases are caused by mutations of various subunits of the nicotinic acetylcholine receptor (RECEPTORS, NICOTINIC) on the postsynaptic surface of the junction. (From Arch Neurol 1999 Feb;56(2):163-7)

The intentional interruption of transmission at the NEUROMUSCULAR JUNCTION by external agents, usually neuromuscular blocking agents. It is distinguished from NERVE BLOCK in which nerve conduction (NEURAL CONDUCTION) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce MUSCLE RELAXATION as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here.

Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc.

A diverse group of metabolic diseases characterized by errors in the biosynthetic pathway of HEME in the LIVER, the BONE MARROW, or both. They are classified by the deficiency of specific enzymes, the tissue site of enzyme defect, or the clinical features that include neurological (acute) or cutaneous (skin lesions). Porphyrias can be hereditary or acquired as a result of toxicity to the hepatic or erythropoietic marrow tissues.

A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topics

Rheumatology
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Enzymes
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...


Searches Linking to this Article