R25 is an intracellular membrane receptor for a snake venom secretory phospholipase A2

FEBS Letters

Poljšak-Prijatelj, Mateja¹  Čopič, Alenka²  Šribar, Jernej²  Gubenšek, Franc²  Križaj, Igor²  Kuret, Jošt¹  Logonder, Uroš² 

[1] Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia;Department of Biochemistry and Molecular Biology, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia

关键词: Ammodytoxin;    Snake venom;    Secretory phospholipase A2;    Presynaptic neurotoxicity;    Intracellular membrane receptor;    Mitochondrion;    Vipera ammodytes ammodytes;    Atx;    ammodytoxin;    AtxC;    ammodytoxin C;    CaM;    calmodulin;    DSS;    disuccinimidyl suberate;    EGFP;    enhanced green fluorescent protein;    ER;    endoplasmic reticulum;    GPI;    glycosylphosphatidylinositol;    G;    group;    K d;    dissociation constant;    PI-PLC;    phosphatidylinositol-phospholipase C;    PM;    plasma membrane;    R25 and R180;    receptors for AtxC in porcine cerebral cortex of 25 and 180 kDa;    respectively;    sPLA2;    secretory PLA2;    sPLA2R;    sPLA2 receptor;   

DOI  :  10.1016/S0014-5793(03)01035-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Ammodytoxin is a presynaptically neurotoxic (β-neurotoxic) snake venom secretory phospholipase A₂ (sPLA₂). We detected a 25 kDa protein which binds the toxin with very high affinity (R25) in porcine cerebral cortex [Vučemilo et al., Biochem. Biophys. Res. Commun. 251 (1998) 209–212]. Here we show that R25 is an integral membrane protein with intracellular localisation. It is the first sPLA₂ receptor known to date that localises to intracellular membranes. Centrifugation on sucrose gradients was used to fractionate porcine cerebral cortex. The subcellular composition of the fractions was determined by following the distribution of organelle-specific markers. The distribution of R25 in the fractions matched the distribution of the mitochondrial marker succinate dehydrogenase, but not the markers for plasma membrane, lysosomes, endoplasmic reticulum, synaptic and secretory vesicles. R25 most likely resides in mitochondria, which are known to be targets for sPLA₂ neurotoxins in the nerve ending and are potentially implicated in the process of β-neurotoxicity.

【 授权许可】

Unknown