1. Cell Signal Transduction and Diseases

2. Introduction: Cell signaling and Signal transduction (1) Cell signaling
(2) Types of cellular signals
(3) Functions
2. Gap junction and diseases
(1) Structure of gap junction
(2) Function of gap junction
(3) Related diseases
3. Receptor-Mediated Signal Transduction and diseases (1) Cell-surface receptors (2) Nuclear receptors (3) Regulatory mechanisms of signal transduction
(4) Disorders and related diseases

3. Introduction: Cell signaling and Signal transduction
(1) Direct Intercellular Communication
Gap Junction
(2) Signaling by plasma-membrane bound molecules
(3) Receptor-Mediated Intercellular communication
Cell-Surface Receptors
Nuclear Receptors
Gap Junction

4. 2. Types of cellular signals
(1) Chemical signals
Hormones, neurotransmitters, growth factors, cytokines;
odor molecules; ATP, active oxygen; drugs, toxins, etc
(2) Physical signals
Light, electronic, mechanic, UV, heat, volume, osmotic, etc
According to the characteristics of signal molecules, it can be divided into two major typies

5. (3) Modes for the function of endogenous signals
Endocrine
Act on a far away organ via blood circulation, seen in most hormones
Paracrine
Act on a nearby target, seen in GFs, CKs, etc
Synaptic: Presynaptic to postsynaptic (neurotransmitters)
Autocrine
Act on itself after secreted, seen in GFs, especially in tumor tissues
Intracrine
Act on itself before secreted, seen in nuclear receptors
Secondary messenger
Ca2+, DAG, IP3, Cer, cAMP, cGMP
Small molecules which are used to transduce information within the cells

6. Microvesicles are membrane-enclosed extracellular vesicles shed from the plasma membrane or derived from the endosomal membrane of cells， which can mediate intercellular communication through transferring the vesicular components to recipient cells.

7. 3. Cell Signal Transduction Pathways --Physiological functions --Metabolism --Cell cycle, growth, differentiation, and apoptosis --Responses to stress --etc.
LPS
TNF
IL-1

8. Gap junction 1. Structure of Gap Junction
Connexins are four-pass transmembrane proteins,
six of which assemble to form a channel, a connexon.
~ 20 different isoforms of connexins in humans and mice

9. 2. Function of Gap Junction
Used by most cells in animal tissues with the exception of a few terminally differentiated cells, such as skeletal muscle cells and blood cells
Allowing inorganic ions and other small water-soluble molecules to pass directly from one cell to the other, thus coupling the cells both electrically and metabolically
In electrically excitable cells such as nerve cells allow action potential to spread rapidly without the delay that occurs at chemical synapses
The sharing of small metabolites and ions provides a mechanism for coordinating the activities of individual cells (metabolic cooperation)

10. 3. Gap Junction in Diseases
Connexin gene mutation and Diseases
Congenital non-syndromatic deafness (Cx26 mutation)
Congenital cataract (Cx50 mutation)
Axonal degeneration of peripheral nerves (Cx32 mutation)
Infertility of females (Cx37)
Gap junction and tumor promotion
-- Gap junction intercellular communication down-regulated
Gap junction and embryogenesis
-- embryo development (Cx43)
-- nutrients transportation (Cx26)
Others

11. Receptor-Mediated Signal Transduction Systems
Receptors:
Cell Surface Receptors;
Nuclear Receptors

12. Cell-surface receptors
1. Process of transmembrane signal transduction
Synthesis and secretion of signaling molecules
Receptor binding and initiation of intracellular signaling pathway
Regulation of cellular metabolism, function, gene expression, etc
Down-regulation or termination of cellular responses
As a general signal transduction process involves the following major approaches:
Any of these steps has problem, the abnormality will occur.

13. 2. Classification of cell-surface receptors
Ion-channel-linked receptors
Involved in rapid synaptic signaling between electrically excitable cells
G-protein coupled receptors (GPCR)
Seven-pass transmembrane protein,
indirectly regulate the activity of a target protein through a trimeric GTP-binding protein (G-protein)
Enzyme-linked receptors
Single-pass transmembrane protein,
function directly as enzyme or directly associated with enzymes they activate
Others