Linked Life Data

15140922

Source:http://linkedlifedata.com/resource/pubmed/id/15140922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2004-5-13
pubmed:abstractText
A novel paralytic mutant, nubian, was identified in a behavioral screen for conditional temperature-sensitive seizure mutants in Drosophila melanogaster. nubian mutants display reduced lifespan, abnormal motor behavior, altered synaptic structure, and defective neurotransmitter release. The nubian mutant disrupts phosphoglycerate kinase (PGK), an enzyme required for ATP generation in the terminal stage of the glycolytic pathway. Consistent with altered ATP generation in nubian animals, brain extracts show a threefold reduction in resting ATP levels compared with controls. Microarray analysis of nubian mutants reveals altered transcription of genes implicated in glucose and lipid metabolism. Disruption of ATP generation in nubian animals is accompanied by temperature-dependent defects in neuronal activity, with initial seizure activity, followed by an activity-dependent loss of synaptic transmission. nubian mutants also display structural defects at the synapse, with larger varicosity size but normal varicosity number, indicating that these synaptic parameters are regulated independently. Both exocytotic (NSF) and endocytotic (dynamin) ATPase/GTPase activity are required for normal synaptic transmission. Biochemical and physiological analyses indicate that synaptic defects in nubian animals are secondary to defective endocytosis, suggesting that endocytotic pathways may be generally more sensitive to altered ATP levels than those used for exocytosis. Alterations in ATP metabolism likely disrupt similar pathways in humans, because PGK deficiency is associated with mental retardation, seizures, and exercise intolerance. Given the behavioral similarities between disruptions of PGK function in Drosophila and humans, the analysis of nubian animals may reveal conserved neuronal responses associated with altered ATP generation within the brain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4518-29
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed-meshheading:15140922-Adenosine Triphosphate, pubmed-meshheading:15140922-Animals, pubmed-meshheading:15140922-Behavior, Animal, pubmed-meshheading:15140922-Chromosome Mapping, pubmed-meshheading:15140922-Drosophila, pubmed-meshheading:15140922-Electrophysiology, pubmed-meshheading:15140922-Endocytosis, pubmed-meshheading:15140922-Female, pubmed-meshheading:15140922-Genetic Testing, pubmed-meshheading:15140922-Larva, pubmed-meshheading:15140922-Male, pubmed-meshheading:15140922-Membrane Proteins, pubmed-meshheading:15140922-Mutagenesis, pubmed-meshheading:15140922-Mutation, pubmed-meshheading:15140922-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15140922-Paralysis, pubmed-meshheading:15140922-Phosphoglycerate Kinase, pubmed-meshheading:15140922-SNARE Proteins, pubmed-meshheading:15140922-Seizures, pubmed-meshheading:15140922-Synapses, pubmed-meshheading:15140922-Synaptic Transmission, pubmed-meshheading:15140922-Synaptic Vesicles, pubmed-meshheading:15140922-Temperature, pubmed-meshheading:15140922-Vesicular Transport Proteins
pubmed:year
2004
pubmed:articleTitle
A Drosophila temperature-sensitive seizure mutant in phosphoglycerate kinase disrupts ATP generation and alters synaptic function.
pubmed:affiliation
The Picower Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't