Abstract
The molecular mechanism of action of presynaptically neurotoxic secreted phospholipases A2 (sPLA2s) has not been fully elucidated. We have recently proposed a model to explain one of the hallmarks of their action - the reduction in endocytosis leading to synaptic vesicle depletion in nerve terminals. Our results speak strongly in favor of a mechanism in which both specific protein-protein interactions and enzymatic activity of the neurotoxic sPLA2 ammodytoxin A (AtxA) are necessary for impairment of clathrin-dependent endocytosis in yeast cells. The reduction of endocytosis was strictly dependent on the enzymatic activity of sPLA2s expressed ectopically in our yeast model cells and was not observedwith the catalytically inactive, non-neurotoxic AtxA-homolog, ammodytin L (AtnL). Here weconfirm the validity of the model in mammalian cells also, by demonstrating that the enzymatically active mutant of AtnL, shown to inhibit endocytosis in yeast, acts as a presynaptically neurotoxic sPLA2 at the mammalian neuromuscular junction.
| Original language | English |
|---|---|
| Article number | e23600 |
| Number of pages | 3 |
| Journal | Communicative and Integrative Biology |
| Volume | 6 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 9 Apr 2013 |
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Keywords
- ammodytin
- ammodytoxin
- endocytosis
- myotoxicity
- neuromuscular activity
- presynaptic neurotoxicity
- secreted phospholipase A
Cite this
}
Neurotoxic phospholipase A2 toxicity model : an insight from mammalian cells. / Vardjan, Nina; Mattiazzi, Mojca; Rowan, Edward G.; Križaj, Igor; Petrovič, Uros̀; Petan, Toni.
In: Communicative and Integrative Biology, Vol. 6, No. 3, e23600, 09.04.2013.Research output: Contribution to journal › Article
TY - JOUR
T1 - Neurotoxic phospholipase A2 toxicity model
T2 - an insight from mammalian cells
AU - Vardjan, Nina
AU - Mattiazzi, Mojca
AU - Rowan, Edward G.
AU - Križaj, Igor
AU - Petrovič, Uros̀
AU - Petan, Toni
PY - 2013/4/9
Y1 - 2013/4/9
N2 - The molecular mechanism of action of presynaptically neurotoxic secreted phospholipases A2 (sPLA2s) has not been fully elucidated. We have recently proposed a model to explain one of the hallmarks of their action - the reduction in endocytosis leading to synaptic vesicle depletion in nerve terminals. Our results speak strongly in favor of a mechanism in which both specific protein-protein interactions and enzymatic activity of the neurotoxic sPLA2 ammodytoxin A (AtxA) are necessary for impairment of clathrin-dependent endocytosis in yeast cells. The reduction of endocytosis was strictly dependent on the enzymatic activity of sPLA2s expressed ectopically in our yeast model cells and was not observedwith the catalytically inactive, non-neurotoxic AtxA-homolog, ammodytin L (AtnL). Here weconfirm the validity of the model in mammalian cells also, by demonstrating that the enzymatically active mutant of AtnL, shown to inhibit endocytosis in yeast, acts as a presynaptically neurotoxic sPLA2 at the mammalian neuromuscular junction.
AB - The molecular mechanism of action of presynaptically neurotoxic secreted phospholipases A2 (sPLA2s) has not been fully elucidated. We have recently proposed a model to explain one of the hallmarks of their action - the reduction in endocytosis leading to synaptic vesicle depletion in nerve terminals. Our results speak strongly in favor of a mechanism in which both specific protein-protein interactions and enzymatic activity of the neurotoxic sPLA2 ammodytoxin A (AtxA) are necessary for impairment of clathrin-dependent endocytosis in yeast cells. The reduction of endocytosis was strictly dependent on the enzymatic activity of sPLA2s expressed ectopically in our yeast model cells and was not observedwith the catalytically inactive, non-neurotoxic AtxA-homolog, ammodytin L (AtnL). Here weconfirm the validity of the model in mammalian cells also, by demonstrating that the enzymatically active mutant of AtnL, shown to inhibit endocytosis in yeast, acts as a presynaptically neurotoxic sPLA2 at the mammalian neuromuscular junction.
KW - ammodytin
KW - ammodytoxin
KW - endocytosis
KW - myotoxicity
KW - neuromuscular activity
KW - presynaptic neurotoxicity
KW - secreted phospholipase A
UR - http://www.scopus.com/inward/record.url?scp=84879108687&partnerID=8YFLogxK
UR - http://www.tandfonline.com/toc/kcib20/current
U2 - 10.4161/cib.23600
DO - 10.4161/cib.23600
M3 - Article
VL - 6
JO - Communicative and Integrative Biology
JF - Communicative and Integrative Biology
SN - 1942-0889
IS - 3
M1 - e23600
ER -