Calmodulin dependence of presynaptic metabotropic glutamate receptor signalling
Calmodulin dependence of presynaptic metabotropic glutamate receptor signalling
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突触前代谢型谷氨酸受体信号传导的钙调蛋白依赖性
DOI：
10.1042/bst027a035
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发表时间：
1999
影响因子：
3.9
通讯作者：
S. Böhm
中科院分区：
文献类型：
--
作者：
V. O'Connor;O. Far;E. Bofill;C. Nanoff;M. Freissmuth;José M. Airas;H. Betz;S. Böhm
肿瘤沿周围神经沿着扩散是许多解剖部位的癌中的常见事件，并且代表了met（淋巴瘤）的另一种机制。有证据表明，一种独特的分子机制可能是肿瘤以这种方式扩散的趋势的原因。我们已经开发了一种新的用于研究人CDL与周围神经组织之间的相互作用的振动模型，并且以前的研究表明，在周围神经组织上培养的恶性口腔上皮CDL向成纤维细胞样的方向发生了明显的形态学变化。细胞通常变为双极并延伸长（10- 2 Opm）突起，与神经中的轴突突起紧密对齐。为了研究这种现象的潜在分子机制，已经进行了神经基质和介质成分的生化操作。的分子相互作用是敏感的蛋白质水解（胰蛋白酶，胰凝乳蛋白酶，木瓜蛋白酶）和洗涤剂extradon（Triton X-100，SDS）的周围神经部分之前，培养的肿瘤细胞。两种处理均导致形态分化的显著的浓度依赖性抑制。细胞在添加EDTA的无钙培养基中培养（IOOphQ对形态分化无影响。在培养基中加入erbstatin（ISpglmI）、cytochnlasin D（lpg/mI）或放线菌酮（Spg/d）抑制形态分化。我们的结论是，恶性口腔上皮细胞与周围神经组织接触的形态分化涉及ncrve中的膜结合蛋白与肿瘤plls表面蛋白之间的离散分子相互作用。这种相互作用是不依赖于钙的，并导致norgatisation的肌动蛋白cytotoxicton，信号通过erbstatin敏感的酪氨酸激酶，并需要my 0蛋白的合成。我们希望能鉴定出肿瘤细胞表面参与这种分化的分子，并继续确定细胞内的促增殖因子介导物。
Tumour spread along periphad nerves is a common event in carcinoma at many anatomical sites, and represents an additional mechanism of met (LstBsis aAer lymphrtic ad haemrtogmous spread. Evidence su~ gesls that a distinctive mol& mechanism may be responsible for the tendency of tumours to spread in this way. We have devdoped a novel in vibo modd for the study of intaaCtions betweem hunour cdl l i and peripheral me tissue, and have previouSry shown that malipant oral epithdial cdls cultured on peripheral nerve tissue dons undcrgo a pronounced morphological Mwentiation towards a fibroblast-like appcdmnce. The cells typically become bipolar and extend long (10-2Opm) processes, closely aligned with the axon buqlles in the nerve. To invedgate the underlying molecular mechanisms of this phenomenon, biochemical manipdations of the nerve substratum and the medium composition have been carried out. The molecular interactions are sensitive to both proteolysis (trypsin, chymotrypsin, papain) and detergent extradon (Triton X-100, SDS) of the peripheral nerve sections prior to culture of the tumour cells. Both treatments lead to a significant, concentrationdependent inhibition of morphological differentiation. Culture of the cells in a calcium-free medium with the addition of EDTA (IOOphQ had no e&ct on morphological differentiation. The inclusion of erbstatin (ISpglmI), cytochnlasin D (lpg/mI) or cycloheximide (Spg/d) in the culturp medium inhibited morphological differentiation. We conclude that the morphofogicai differentiation of malignant oral epithelial cells in contact with peripheral nerve tissue involves a discrete moleatlar interaction between membrane-bound proteins in the ncrve and proteins on the surface of the tumour plls. This interaction is calcium-independent and leads to norgatisation of the actin cytoskelcton, signalled through an erbstatin-sensitive tyrosine kinsse and requiring & my0 protein synthesis. We hope to identify the molecules on the tumour cell surface that are involved in this form of differcntiatipn and to continue to define intracdlular mediators of the phmommon