Linked Life Data

10407024

Source:http://linkedlifedata.com/resource/pubmed/id/10407024

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1999-8-2
pubmed:abstractText
Rab3A and rab3C are GTP-binding proteins of synaptic vesicles that regulate vesicle exocytosis. Rabphilin is a candidate rab3 effector at the synapse because it binds to rab3s in a GTP-dependent manner, it is co-localized with rab3s on synaptic vesicles, and it dissociates with rab3s from the vesicles during exocytosis. Rabphilin contains two C(2) domains, which could function as Ca(2+) sensors in exocytosis and is phosphorylated as a function of stimulation. However, it is unknown what essential function, if any, rabphilin performs. One controversial question regards the respective roles of rab3s and rabphilin in localizing each other to synaptic vesicles: although rabphilin is mislocalized in rab3A knock-out mice, purified synaptic vesicles were shown to require rabphilin for binding of rab3A but not rab3A for binding of rabphilin. To test whether rabphilin is involved in localizing rab3s to synaptic vesicles and to explore the functions of rabphilin in regulating exocytosis, we have now analyzed knock-out mice for rabphilin. Mice that lack rabphilin are viable and fertile without obvious physiological impairments. In rabphilin-deficient mice, rab3A is targeted to synaptic vesicles normally, whereas in rab3A-deficient mice, rabphilin transport to synapses is impaired. These results show that rabphilin binds to vesicles via rab3s, consistent with an effector function of rabphilin for a synaptic rab3-signal. Surprisingly, however, no abnormalities in synaptic transmission or plasticity were observed in rabphilin-deficient mice; synaptic properties that are impaired in rab3A knock-out mice were unchanged in rabphilin knock-out mice. Our data thus demonstrate that rabphilin is endowed with the properties of a rab3 effector but is not essential for the regulatory functions of rab3 in synaptic transmission.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5834-46
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10407024-Adaptor Proteins, Signal Transducing, pubmed-meshheading:10407024-Animals, pubmed-meshheading:10407024-Brain, pubmed-meshheading:10407024-Cerebral Cortex, pubmed-meshheading:10407024-Cloning, Molecular, pubmed-meshheading:10407024-DNA Primers, pubmed-meshheading:10407024-Exocytosis, pubmed-meshheading:10407024-GTP-Binding Proteins, pubmed-meshheading:10407024-Mice, pubmed-meshheading:10407024-Mice, Knockout, pubmed-meshheading:10407024-Models, Neurological, pubmed-meshheading:10407024-Nerve Tissue Proteins, pubmed-meshheading:10407024-Neuronal Plasticity, pubmed-meshheading:10407024-Neurotransmitter Agents, pubmed-meshheading:10407024-Polymerase Chain Reaction, pubmed-meshheading:10407024-Restriction Mapping, pubmed-meshheading:10407024-Subcellular Fractions, pubmed-meshheading:10407024-Synapses, pubmed-meshheading:10407024-Synaptic Vesicles, pubmed-meshheading:10407024-Vesicular Transport Proteins, pubmed-meshheading:10407024-rab GTP-Binding Proteins, pubmed-meshheading:10407024-rab3 GTP-Binding Proteins
pubmed:year
1999
pubmed:articleTitle
Rabphilin knock-out mice reveal that rabphilin is not required for rab3 function in regulating neurotransmitter release.
pubmed:affiliation
Abteilung Molekulare Neurobiologie, Max-Planck-Institut für Experimentelle Medizin, 37075 Goettingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't