GPI-Anchored Proteinとマウス神経細胞のテタヌストキシンに対する高感受性

抄録

Tetanus neurotoxin (TeNT) produced by Clostridium tetani specifically cleaves VAMP/synaptobrevin (VAMP) in central neurons, thereby causing inhibition of neurotransmitter release and ensuring spastic paralysis. Although polysialogangliosides act as components of the neurontoxin binding sites on neurons, evidence has accumulated indicating that a protein moiety is implicated as a receptor of TeNT. We have observed that treatment of cultured mouse neuronal cells with the phosphatidylinositol-specific phospholipase C (PIPLC) inhibited TeNT-induced cleavage of VAMP. Also, we have shown that the blocking effects of TeNT on neuroexocytosis can be prevented by incubation of Purkinje Cell preparation with PIPLC. In addition, treatment of cultured mouse neuronal cells with filipin, which disrupt clustering of GPI-anchored proteins in lipid refts, prevented intraneuronal VAMP cleavage by TeNT. Our results demonstrate that high sensitivity of neurons to TeNT requires rafts and one or more GPI-anchored protein(s) which act(s) as a pivotal receptor for neurotoxin. [Jpn J Physiol 54 Suppl:S142 (2004)]