A presynaptically toxic secreted phospholipase A2 is internalized into motoneuron-like cells where it is rapidly translocated into the cytosol
Articolo
Data di Pubblicazione:
2008
Citazione:
A presynaptically toxic secreted phospholipase A2 is internalized into motoneuron-like cells where it is rapidly translocated into the cytosol / Z.J. Praznikar, L. Kovacic, E.G. Rowan, R. Romih, P. Rusmini, A. Poletti, I. Krizaj, J. Pungercar. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - 1783:6(2008 Jun), pp. 1129-1139.
Abstract:
The molecular mechanism of the presynaptic toxicity of secreted phospholipase A2 (sPLA2) neurotoxins, including that of ammodytoxin A (AtxA), has not been resolved. Here we report the action of AtxA on mouse motoneuron-like cells, on which it induced characteristic neurotoxic effects on synaptic vesicles and on the reorganization of F-actin. AtxA also released fatty acids from the plasmalemma. Its significantly less neurotoxic V31W mutant showed similar effects on cells but with a much higher rate of hydrolysis than the wild-type, indicating that high enzymatic activity alone is not sufficient for the observed effects. The neurotoxic action was observed by confocal microscopy of a fluorescently labelled AtxA and by electron microscopy of a nanogold-labelled toxin. The Atx-binding proteins were tagged by a photo-cross-linking reagent conjugated to the toxin. AtxA was taken up rapidly by the cells, where it interacted within minutes with calmodulin and 14-3-3 proteins in the cytosol. These data demonstrate, for the first time, the translocation of an sPLA2 from the extracellular space into the cytosol of a cell. Such an event may thus be important in explaining the action of a range of homologous endogenous sPLA2 enzymes in mammals whose roles in various cellular processes are not yet completely understood
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Ammodytoxin; Cytosolic protein; Motoneuron; Neurotoxicity; Secreted phospholipase A2; Synaptic vesicle
Elenco autori:
Z.J. Praznikar, L. Kovacic, E.G. Rowan, R. Romih, P. Rusmini, A. Poletti, I. Krizaj, J. Pungercar
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