Vesicle exocytosis stimulated by alpha-latrotoxin is mediated by latrophilin and requires both external and stored Ca2+
| Autor: | H Matsushita, Anthony C. Ashton, Bazbek Davletov, W D Hirst, Vera G. Lelianova, Yuri A. Ushkaryov, Frederic A. Meunier, Graham P. Wilkin, J. O. Dolly |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Botulinum Toxins Reserpine Receptors Peptide G protein Phosphodiesterase Inhibitors Latrotoxin Neuromuscular Junction Spider Venoms Nerve Tissue Proteins Biology Norepinephrine secretion General Biochemistry Genetics and Molecular Biology Exocytosis chemistry.chemical_compound Norepinephrine Animals Inositol Secretion Estrenes Molecular Biology Calcimycin Glycoproteins General Immunology and Microbiology Phospholipase C Ionophores General Neuroscience Neuropeptides Rana esculenta Depolarization Pyrrolidinones Rats Biochemistry chemistry Type C Phospholipases COS Cells Biophysics Calcium Synaptosomes Research Article |
| Zdroj: | The EMBO journal. 17(14) |
| ISSN: | 0261-4189 |
| Popis: | α‐Latrotoxin (LTX) stimulates massive neurotransmitter release by two mechanisms: Ca 2+ ‐dependent and ‐independent. Our studies on norepinephrine secretion from nerve terminals now reveal the different molecular basis of these two actions. The Ca 2+ ‐dependent LTX‐evoked vesicle exocytosis (abolished by botulinum neurotoxins) is 10‐fold more sensitive to external Ca 2+ than secretion triggered by depolarization or A23187; it does not, however, depend on the cation entry into terminals but requires intracellular Ca 2+ and is blocked by drugs depleting Ca 2+ stores and by inhibitors of phospholipase C (PLC). These data, together with binding studies, prove that latrophilin, which is linked to G proteins and inositol polyphosphate production, is the major functional LTX receptor. The Ca 2+ ‐independent LTX‐stimulated release is not inhibited by botulinum neurotoxins or drugs interfering with Ca 2+ metabolism and occurs via pores in the presynaptic membrane, large enough to allow efflux of neurotransmitters and other small molecules from the cytoplasm. Our results unite previously contradictory data about the toxin9s effects and suggest that LTX‐stimulated exocytosis depends upon the co‐operative action of external and intracellular Ca 2+ involving G proteins and PLC, whereas the Ca 2+ ‐independent release is largely non‐vesicular. |
| Databáze: | OpenAIRE |
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