Cell Signal Transduction and Diseases

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

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

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

(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

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.

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

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

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)

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

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

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.

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