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1、,返回目录,返回主页,上一页,细胞的信息处理途径类比计算机的处理网络,信号传导通路具有级联放大作用,SIGNAL TRANSDUCTION: AMPLIFICATION,第一节 概 述 Introduction,Fundamental Concepts,细胞对外界信号的反应是生命的特征之一。 The ability of cells to receive and act on signals from beyond the plasma membrane is fundamental to life.,细菌与单细胞生物直接对环境刺激作出反应,而多细胞生物尤其是高等生物则需要广泛的细胞间信号交流
2、。 Bacteria and single cell organisms usually respond to environmental changes directly. While multicellular organism cells with different functions need to exchange a wide variety of intercellular signals. 植物主要对生长激素及光线变化等信号起反应。Plant cells respond to growth hormones and to variations in sunlight., 动物
3、细胞则主要对内环境的各种变化作出反应,如离子及各代谢物浓度的感应,各器官组织代谢活性的相互协调,以及胚胎细胞发育的精确调控等。 Animal cells exchange information about the concentrations of ions and glucose in extracellular fluids, the interdependent metabolic activities taking place in different tissues, and, in an embryo, the correct placement of cells during
4、development., 以上的各种内外信号均由相应的信息物质(分子)携带,可以被特定的受体识别,通过一定方式传递到细胞内部并引起细胞内的化学改变,从而产生生物效应。这就是细胞的信号转导。 In all these cases, the signal represents information that is detected by specific receptors and converted to a cellular response, which always involves a chemical process. This conversion of information
5、into a chemical change, signal transduction, is a universal property of living cells.,细胞信号转导的基本过程如下: The common process of signal transduction follows the pathway list below:,特定细胞合成并分泌信号分子 信号分子通过扩散或血液循环到达靶细胞 靶细胞上的受体识别结合信号 通过一系列化学反应将信号转导至细胞内 产生特定生物学效应,some specific cells synthesize and secrete signal
6、 molecules signal reach to target cells through diffusion or blood circulation the specific receptor on target cells recognize and bind the signal information are convert to intracellular response via a series of chemical reactions corresponding biological effects are generated,细胞通讯(cell communicati
7、on):指一个细胞发出的信息通过介质传递到另一个细胞产生相应反应的过程。 细胞通讯主要有三种方式: 1 细胞间隙连接 2 膜表面分子接触通讯 3 化学通讯,信号转导(signal transduction): 指外界信号(如光、电、化学分子)与细胞细胞表面受体作用,通过影响细胞内信使的水平变化,进而引起细胞应答反应的一系列过程。 不同信号转导通路之间存在交差对话(cross talk),细胞间隙连接,膜表面分子接触通讯,化学通讯,Cell-cell communication: no signal molecule,Communication between neighboring cells
8、: no signal molecule is needed, direct link (desmosomes, tunneling nanotubules) between the cytoplasms (metabolism of the cells is coordinated),Change in intracytoplasmic Ca+ ion concentration spreads from one cell to other in case of desmosomally linked cells,Cell-cell communication: signal molecul
9、es,Humoral communication between cells: endocrine and paracrine contact,Membrane penetrating (small, hydrophobic)molecules, cytoplasmic receptors, direct effect on gene activity,Hydrophilic molecules,cell-surface receptors, intracellular signaling second messengers sophisticated signaling and signal
10、-amplification mechanisms,Definitions,The molecules, produced by the signaling cell (hormones, cytokines, growth factors, chemoattractants, neurotransmitters, etc.) are usually called ligands. The molecules that detect them and interact with them with high specificity and high affinity are called re
11、ceptors. Receptors are located in the cytoplasm or on the plasmamembrane. The receptors we discuss today are either transcription factors or able to activate transcription factors by intracellular signaling mechanisms.,Hormones,Endocrine signaling: hormons are produced by endocrine glands, the extra
12、cellular signal is secreted into the blood stream, their effect is very specific Paracrine signaling molecules might circulate outside the blood vessels Autocrine factors stimulate the producing cells: in case of mitogenic factors it could lead to unlimited proliferation,Signaling: 6-7 steps product
13、ion of the signal, export (secretion), transport, detection (receptor), intracellular signal- transduction, metabolic response,termination of the signal: decomposition of the molecule(s) participating in the signal,间隙连接(Gap Junction),两个相邻的细胞间存在着一种特殊的由蛋白质构成的结构连接子(Connexon)。连接子两端分别嵌入两个相邻的细胞,形成一个亲水性孔道。
14、这种孔道允许自由交换分子量为1500道尔顿以下的水溶性分子。这种直接交换的意义在于相邻的细胞可以共享小分子物质,因此可以快速和可逆地促进相邻细胞对外界信号的协同反应。连接子为一个多基因家庭,现已发现12个成员。在肿瘤生长和创伤愈合等过程中都观察到某些类型连接子表达的变化。因此,连接子可能对细胞的生长、分化、定位及细胞形态的维持具有重要意义。 分布:除骨骼肌细胞及循环血细胞外的细胞之间。,膜表面分子接触通讯,细胞都有众多的分子分布于膜的外表面。这些分子或为蛋白质,或为糖蛋白。这些表面分子作为细胞的触角,可以与相邻细胞的膜表面分子特异性地相互识别和相互作用,以达到功能上的相互协调。这种细胞通讯方式
15、称为膜表面分子接触通讯。膜表面分子接触通讯也属于细胞间的直接通讯,最为典型的例子是T淋巴细胞与B淋巴细胞的相互作用。,化学通讯,细胞可以分泌一些化学物质蛋白质或小分子有机化合物至细胞外,这些化学物质作为化学信号(chemical signaling)作用于其它的细胞(靶细胞),调节其功能,这种通讯方式称为化学通讯。化学通讯是间接的细胞通讯,即细胞间的相互联系不再需要它们之间的直接接触,而是以化学信号为介质来介导的。根据化学信号分子可以作用的距离范围,将其分为三类,返回目录,返回主页,返回目录,返回主页,返回目录,返回主页,返回目录,返回主页,返回目录,返回主页,返回目录,返回主页,膜表面分子接
16、触通讯,细胞都有众多的分子分布于膜的外表面。这些分子或为蛋白质,或为糖蛋白。这些表面分子作为细胞的触角,可以与相邻细胞的膜表面分子特异性地相互识别和相互作用,以达到功能上的相互协调。这种细胞通讯方式称为膜表面分子接触通讯。膜表面分子接触通讯也属于细胞间的直接通讯,最为典型的例子是T淋巴细胞与B淋巴细胞的相互作用。,返回目录,返回主页,化学通讯,细胞可以分泌一些化学物质蛋白质或小分子有机化合物至细胞外,这些化学物质作为化学信号(chemical signaling)作用于其它的细胞(靶细胞),调节其功能,这种通讯方式称为化学通讯。化学通讯是间接的细胞通讯,即细胞间的相互联系不再需要它们之间的直接接触,而是以化学信号为介质来介导的。根据化学信号分子可以作用的距离范围,将其分为三类,化学信号分子的种类及特性,内分泌(endocrine)系统的化学信号称为激素,作用距离最远。 自分泌(autocrine)神经系统的化学信号神经递质(neural transmitter),作用距离最近。 旁分泌(paracrine)系统的化学信