A peptide that mimics the carboxy‐terminal domain of SNAP‐25 blocks Ca2+‐dependent exocytosis in chromaffin cells

FEBS Letters

Montal, Mauricio¹  Gutiérrez, Luis M.²  Viniegra, Salvador²  Cánaves, Jaume M.¹  Ferrer-Montiel, Antonio V.¹  Reig, Juan A.² 

[1] Department of Biology, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA 92083-0366, USA;Departamento de Neuroquímica, Instituto de Neurociencias, Universidad de Alicante, Ap. 374, Alicante 03080, Spain

关键词: Vesicle fusion;    Adrenomedullary cell;    Catecholamine secretion;    SNARE;    SNAP-25;    SNAP-25;    synaptosomal associated protein of 25 kDa;    BoTx;    botulinum neurotoxin;    SNAP;    soluble N-ethylmaleimide-sensitive fusion protein attachment protein;    SNARE;    SNAP receptor;   

DOI  :  10.1016/0014-5793(95)00944-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

SNAP-25, a synaptosomal associated membrane protein of 25 kDa, participates in the presynaptic process of vesicle-plasma membrane fusion that results in neurotransmitter release at central nervous system synapses. SNAP-25 occurs in neuroendocrine cells and, in analogy to its role in neurons, has been implicated in catecholamine secretion, yet the nature of the underlying mechanism remains obscure. Here we use an anti-SNAP-25 monoclonal antibody to show that SNAP-25 is localized at the cytosolic surface of the plasma membrane of chromaffin cells. This antibody inhibited the Ca²⁺-evoked catecholamine release from digitonin-permeabilized chromaffin cells in a time- and dose-dependent manner. Remarkably, a 20-mer synthetic peptide representing the sequence of the C-terminal domain of SNAP-25 blocked Ca²⁺-dependent catecholamine release with an IC₅₀ = 20 μM. The inhibitory activity of the peptide was sequence-specific as evidenced by the inertness of a control peptide with the same amino acid composition but random order. The C-terminal segment of SNAP-25, therefore, plays a key role in regulating Ca²⁺-dependent exocytosis, presumably mediated via interactions with other protein components of the fusion complex.

【 授权许可】

Unknown