•第二节

细胞通讯与信号传递• cell communication and

• signal transduction

CELL COMMUNICATION

Cells communicate with one another using chemical signals. These signals are essential to regulation and coordination of cell activities. For a receiving cell, the three stages of signaling are reception, transduction, and response.

• Overview of cell signaling

Sex hormone

ectohormone(5) 外激素ectohormone•信息素由外分泌腺通过导管离开身体刺激另一个体的靶细胞。

昆虫的信息素

警戒素

性息素或性外激素

雌蛾最大量的分泌可引来 100 万只雄蛾。

接受器如何？

触角是接受天线，能感受气味分子发射的红外光谱。

卡达汉的故事

corruption

blankly

Cell signaling can affect virtually every aspect of

cell structure and function:

Activation of enzyme activity;

Change in cytoskeletal organization;

Change in ion permeability;

Initiation of DNA synthesis;

Activation or repression of gene expression.

4

Importance of Signal Transduction

Signal Transduction

Development

Cell Growth

Apoptosis

Immunology

Metabolism

Four features of signal-transducing systems

枪响 - 交感神经 肾上腺髓

质肾上腺素 肌肉细胞

糖原分解

内质网

1 磷酸 葡萄糖

6 磷酸葡萄糖

葡萄糖胞质糖酵解线立体 3 羧酸循环ATP

肝细胞

糖原分解

内质网

1 磷酸 葡萄糖6 磷酸葡萄糖葡萄糖

跨膜运输

肌肉细胞

与 G 蛋白偶联的膜受体

环化腺苷酸增高

最终活化磷酸化酶

乳酸丙酮酸过线立体膜

放大阶式级联

Signaling pathways consist of a series of steps

signal magnification

1. Recognition of the stimulus by a specific plasma membrane receptor.

2. Transfer of a signal across the plasma membrane.

3. Transmission of the signal to effector molecules within the cell, which causes a change in cellular activities.

4. Cessation of the cellular response due to inactivation of the signal

molecule.

• The Nervous and Endocrine Systems • The pituitary 脑垂体 gland (often called

the master gland) is located in a small bony cavity at the base of the brain. A stalk links the pituitary to the hypothalamus, which controls release of pituitary hormones. The pituitary gland has two lobes: the anterior and posterior lobes. The anterior pituitary is glandular.

•The endocrine system in females and males. Image from Purves et al., Life: The Science of Biology, 4th Edition,

• The hypothalamus contains neurons that control releases from the anterior pituitary. Seven hypothalamic hormones are released into a portal system connecting the hypothalamus and pituitary, and cause targets in the pituitary to release eight hormones.

•The location and roles of the hypothalamus and pituitary glands. Images from Purves et al., Life: The Science of Biology, 4th Edition,

• Growth hormone (GH) is a peptide anterior pituitary hormone essential for growth. GH-releasing hormone stimulates release of GH. GH-inhibiting hormone suppresses the release of GH. The hypothalamus maintains homeostatic levels of GH. Cells under the action of GH increase in size (hypertrophy肥大 , 过度生长 , 过度增大 ) and number (hyperplasia 增生 , 数量性肥大 ). GH also causes

• increase in bone length and thickness by deposition of cartilage 软骨 at the ends of bones. During adolescence, sex hormones cause replacement of cartilage by bone, halting further bone growth even though GH is still present. Too little or too much GH can cause dwarfism or gigantism, respectively.

• Hypothalamus receptors monitor blood levels of thyroid hormones. Low blood levels of Thyroid-stimulating hormone (TSH)cause the release of TSH-releasing hormone from the hypothalamus, which in turn causes the release of TSH from the anterior pituitary.

• TSH travels to the thyroid where it promotes production of thyroid hormones, which in turn regulate metabolic rates and body temperatures.

• Hypothalamus release TSH (Thyroid-stimulating hormone ) -releasing hormone

• TSH-releasing hormone causes anterior pituitary release TSH (Thyroid-stimulating hormone ).

• TSH thyroid promotes production of thyroid hormones

• thyroid hormones metabolic rates and body temperatures.

• Gonadotropins 促性腺激素 and prolactin催乳激素 are also secreted by the anterior pituitary. Gonadotropins (which include follicle-stimulating hormone, FSH, and luteinizing 促黄体 hormone, LH) affect the gonads 生殖腺 by stimulating gamete formation and production of sex hormones. Prolactin is secreted near the end of pregnancy and prepares the breasts for milk production.

• The Posterior Pituitary• The posterior pituitary stores and

releases hormones into the blood. Antidiuretic 抗利尿剂 hormone (ADH)and oxytocinare 催产素produced in the hypothalamus and transported by axons to the posterior pituitary where they are dumped into the blood.

• ADH controls water balance in the body and blood pressure. Oxytocin 催产素 is a small peptide hormone that stimulates uterine contractions during childbirth.

• Other Endocrine Organs

• The Adrenal Glands • Each kidney has an adrenal gland located

above it. The adrenal gland is divided into an inner medulla and an outer cortex. The medulla synthesizes amine hormones, the cortex secretes steroid hormones.

• The adrenal medulla consists of modified neurons that secrete two hormones: epinephrine and norepinephrine. Stimulation of the cortex by the sympathetic nervous system 交感神经 causes release of hormones into the blood to initiate the "fight or flight" response.

• The adrenal cortex produces several steroid hormones in three classes: mineralocorticoids 盐皮质激素 , glucocorticoids 糖皮质激素 , and sex hormones. Mineralocorticoids maintain electrolyte balance.

• Glucocorticoids produce a long-term, slow response to stress by raising blood glucose levels through the breakdown of fats and proteins; they also suppress the immune response and inhibit the inflammatory 炎性的 response.

•The structure of the kidney as relates to hormones. Image from Purves et al., Life: The Science of Biology, 4th Edition,

• The thyroid gland is located in the neck. Follicles 滤泡 in the thyroid secrete thyroglobulin 甲状腺球蛋白 , a storage form of thyroid hormone.

• Thyroid stimulating hormone (TSH) from the anterior pituitary causes conversion of thyroglobulin into thyroid hormones T4 and T3. Almost all body cells are targets of thyroid hormones.

• Thyroid hormone increases the overall metabolic rate, regulates growth and development as well as the onset of sexual maturity. Calcitonin is also secreted by large cells in the thyroid; it plays a role in regulation of calcium.

• The Pancreas• The pancreas contains exocrine

cells that secrete digestive enzymes into the small intestine and clusters of endocrine cells (the pancreatic islets). The islets secrete the hormones insulin and glucagon, 胰高血糖素 which regulate blood glucose levels.

• After a meal, blood glucose levels rise, prompting the release of insulin, which causes cells to take up glucose, and liver and skeletal muscle cells to form the carbohydrate glycogen.

• As glucose levels in the blood fall, further insulin production is inhibited. Glucagon 胰高血糖素 causes the breakdown of glycogen into glucose, which in turn is released into the blood to maintain glucose levels within a homeostatic range.

• Glucagon 胰高血糖素 production is stimulated when blood glucose levels fall, and inhibited when they rise.

• Diabetes results from inadequate levels of insulin. Type I diabetes is characterized by inadequate levels of insulin secretion, often due to a genetic cause. Type II usually develops in adults from both genetic and environmental causes. Loss of response of targets to insulin rather than lack of insulin causes this type of diabetes.

• Diabetes causes impairment in the functioning of the eyes, circulatory system, nervous system, and failure of the kidneys. Diabetes is the second leading cause of blindness in the US. Treatments involve daily injections of insulin, monitoring of blood glucose levels and a controlled diet.

• Other Chemical Messengers

• Interferons are proteins released when a cell has been attacked by a virus

. They cause neighboring cells to produce antiviral proteins. Once activated, these proteins destroy the virus.

• Prostaglandins 前列腺素 are fatty acids that behave in many ways like hormones. They are produced by most cells in the body and act on neighboring cells.

• Pheromones 信息素 , 外激素 are chemical signals that travel between organisms rather than between cells within an organism. Pheromones are used to mark territory, signal prospective mates, and communicate. The presence of a human sex attractant/pheromone has not been established conclusively.

• Biological Cycles

• Biological cycles ranging from minutes to years occur throughout the animal kingdom. Cycles involve hibernation 冬眠

• , mating behavior, body temperature and many other physiological processes.

• Rhythms or cycles that show cyclic changes on a daily (or even a few hours) basis are known as circadian 生理节奏的 rhythms. Many hormones, such as ACTH-cortisol, TSH, and GH show circadianrhythms( 二十四小时节奏 ,生物钟 . )

• The menstrual cycleis controlled by a number of hormones secreted in a cyclical fashion. Thyroid secretion is usually higher in winter than in summer. Childbirth is hormonally controlled, and is highest between 2 and 7 AM.

• Internal cycles of hormone production are controlled by the hypothalamus, specifically the suprachiasmic nucleus (SCN). According to one model, the SCN is signaled by messages from the light-detecting retina of the eyes.The SCN signals the pineal gland in the brain to signal the hypothalamus, etc.

Hypothalamus 下丘脑

pituitary 垂体

thyroid 甲状腺

一、细胞通讯与细胞识别（一）细胞通讯1 分泌化学信号

• 2 膜接触依赖性通讯• 3 间隙连接

1 分泌化学信号• (1) 内分泌（ endocrine ）• (2) 旁分泌 (paracrine)

• (3) 自分泌 (autocrine)• (4) neurotransmitters

• (5) 外激素 ectohormone

• General schemes of intercellular signaling

•(1) 内分泌（ endocrine ）

•(2) 旁分泌(paracrine)

如旁泌素（ FGF ）

（ TGF ）

•(1) 内分泌（ endocrine ） (2) 旁分泌 (paracrine)

•(3) 自分泌 (autocrine) (4) neurotransmitters

(4) neurotransmitters

• 内分泌

靶细胞信号激素类物质

血管

• 旁分泌

信号类

引起胞内一系列生理生化反

应引起胞内一系列生理生化反

应

• 自分泌

信号类引起胞内一系列生

理生化反应

2 膜接触依赖性通讯

•3 间隙连接

( 二 ) 细胞识别与信号通路

signal transduction pathways细胞识别的概念

Signal molecules bind to receptors on the membrane or inside the cell. Receptors activate various kinds of signal transduction pathways, which regulate activities in the cytoplasm and gene transcription in the nucleus.

The cell targeted by a particular signal has a receptor molecule complementary to the signal molecule, or ligand. The ligand fits like a key in a lock and triggers a change in the receptor molecule.

Signal transduction converts the change in the receptor to a form that can bring about a cellular response. This might involve a series of steps-- a signal-transduction pathway-- that alters and amplifies the change.

In the third stage of cell signaling, the transduction process brings about a cellular response. This can be any of many different cellular activities, such as activation of a certain enzyme, rearrangement of the cytoskeleton, or activation of specific genes.

•A 细胞和细胞的识别•1 同种同类 • 血小板•2 同种异类 • 精卵•3 异种异类 • 细菌 真菌感染•4 异种同类 • 器官移植

B 细胞和大分子之间的识别

1 、细胞的信号分子•（ 1 ） . 亲脂•甾类激素和甲状腺素•（ 2 ） . 亲水•神经递质 生长因子 大多数激素

（ 3 ）气体分子

（三）细胞的信号分子与受体Signal Molecules and Receptors

Signal molecules:

Odorant

Pheromones

tastants

2 、受体

Receptors that are plasma-membrane proteins usually affect the cell through multistep signal-transduction pathways. These pathways allow for amplification of signals and signal coordination and regulation.

Most signal molecules act on target cells by binding to receptors in the cell membrane. There are several kinds of membrane receptors. Some signal molecules enter target cells and bind to intracellular receptors in the cytoplasm.

Receptors include two classes:

ligand 和 receptor 不是简单的一对一的关系

不同靶细胞的不同 receptor 可以应答相同的ligand ，但靶细胞的反应不同

同种信号会引起不同细胞的不同响应。

乙酰胆碱引起 骨骼肌细胞收缩

心肌细胞舒张

分泌细胞分泌

同一靶细胞不同 receptor 应答不同 ligand 却有相同的效应。

Different cells can respond differently to the same extracellular signal molecule

Various responses induced by neurotramsmitter acetylcholine

Two-dimensional representation of a “composite”transmembrane receptor showing the approximate sites of a number of mutations responsible for causing human disease