Increased intracellular calcium is required for neurite outgrowth induced by a synthetic peptide ligand of NCAM

FEBS Letters

Rønn, Lars C.B.²  Holm, Arne¹  Dissing, Steen³  Bock, Elisabeth²  Berezin, Vladimir² 

[1] Chemistry Department, Royal Agricultural and Veterinary University, Thorvaldsensvej 40, 1871 Frederiksberg, Denmark;Protein Laboratory, Institute of Molecular Pathology, School of Medicine, University of Copenhagen, Panum Institute 6.2., Blegdamsvej 3, DK-2200 Copenhagen N, Denmark;Division of Cell Physiology, Department of Medical Physiology, School of Medicine, University of Copenhagen, Panum Institute 12.6., Blegdamsvej 3, DK-2200 Copenhagen N, Denmark

关键词: Calcium;    Combinatorial chemistry;    Fura2;    Imaging;    Neural cell adhesion molecule;    Neurite outgrowth;    AgaTxTK;    ω-agatoxin TK;    BSA;    bovine serum albumin;    CgTx MVIIA;    ω-conotoxin MVIIA;    FBS;    fetal bovine serum;    HS;    horse serum;    Ig;    immunoglobulin;    NCAM;    neural cell adhesion molecule;    VDCC;    voltage-dependent calcium channel;   

DOI  :  10.1016/S0014-5793(02)02644-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have recently identified a synthetic peptide, termed C3, capable of binding the first immunoglobulin-like module of neural cell adhesion molecule (NCAM) by means of combinatorial chemistry and shown that this NCAM ligand promotes neurite outgrowth. By means of single cell calcium imaging using the calcium-sensitive probe fura-2-acetomethyl ester, we here show that the C3-peptide induced an increase in intracellular calcium in primary hippocampal neurons and PC12-E2 cells, presumably requiring mobilization of calcium from both extracellular and intracellular stores. We further observed that C3-induced neurite outgrowth was inhibited by antagonists of voltage-dependent calcium channels as well as by an inhibitor of intracellular calcium mobilization, TMB-8. These findings demonstrate at the single cell level that a synthetic NCAM ligand directly can induce an increase in intracellular calcium and suggest that NCAM-dependent neurite outgrowth requires calcium mobilization from both extracellular and intracellular calcium stores. Thus, the C3-peptide may be regarded as a useful tool for the study of NCAM-dependent signal transduction. Furthermore, the peptide may be of considerable therapeutical interest for the treatment of neurodegenerative disorders.

【 授权许可】

Unknown