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Title: Identification of a new binding protein for crotoxin and other neurotoxic phospholipase A sub 2 s on brain synaptic membranes

Journal Article · · Biochemistry; (United States)
OSTI ID:5559096
 [1];  [2]
  1. National Taiwan Univ., Taipei (Taiwan)
  2. National Taiwan Univ., Taipei (Taiwan) Academia Sinica, Taipei (Taiwan)

Crotoxin and other neurotoxic phospholipase A{sub 2}s exert neurotoxicity by acting primarily at the presynaptic level. Strong binding of crotoxin and several other to synaptic membranes has been demonstrated previously. In this study the authors used simple chemical cross-linking techniques to identify the neuronal membrane molecules involved in the binding of these toxins. After {sup 125}I-crotoxin had bound to synaptosomes from guinea pig brain, treatment with disuccinimidyl suberate, disuccinimidyl dithiobis(propionate) or ethylene glycol bis(succinimidyl succinate) resulted in the formation of a predominant radioactive conjugate of {approximately}60 kDa, which was different from the conjugate formed by photoaffinity labeling technique in a previous report. The membrane component in the conjugate was shown to be a single-chain protein {approximately}45 kDa. In subfractions of synaptosomes, this binding protein was mostly found in the synaptic membrane fraction and was not present in the mitochondrial fraction. Plasma membranes from several nonneural tissues also did not contain this binding protein. Unmodified crotoxin inhibited the formation o this adduct with an IC{sub 50} of around 1 {times} 10{sup {minus}8} M. Mojave toxin and some other phospholipase A{sub 2}s were also highly inhibitory to this conjugation, and notexin and others were less effective, while {beta}-bungarotoxin and pancreatic PLA{sub 2} were totally ineffective. They concluded that a new protein of 45 kDa specifically present in neuronal membranes is another major molecule responsible for the binding of crotoxin and other phospholipase A{sub 2}s.

OSTI ID:
5559096
Journal Information:
Biochemistry; (United States), Vol. 30:48; ISSN 0006-2960
Country of Publication:
United States
Language:
English

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