Cell Signaling

（瞎写的 不要在意qwq）

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15a Signaling Overview

Cell signaling

Also known as cell-cell communication. Governs the basic activities of cells and coordinates multiple-cell actions. A signal is an entity that codes or conveys information. Biological processes are complex molecular interactions that involve a lot of signals. The ability of cells to perceive and correctly respond to their micro-environment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis.

Different Cell Types are determined by Regulating Genes and Protein Activities, but genes and protein activities may need to Change depending on Environmental Conditions. Signals change cell behaviors in response to changed environments.

Errors in signaling interactions and cellular information processing may cause diseases such as cancer, autoimmunity, and diabetes.

Examples:

- Signals in the human body in response to seeing a gun - cells in different parts of the body need to communicate with each other, “flight or fight.”

- Signals between bacteria change behavior when living in waterways vs. in the human intestine - bacteria coordinate & communicate with each other to get host.

Signal Transduction

Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.

Signal Transduction converts a message from one form into another as the message is passed from one place to another - converting a signal from the outside world to an intracellular signal that changes the cell’s behavior.

Cellular Signal Transduction

Extracellular signal: upstream of the receptor

Target protein: downstream of the receptor

Target Proteins

- (in)activated - by (de)phosphorylation or allosteric regulation, etc.

If the target protein is an enzymes - no need to be transcribed, just turned on or down, the response is rapid; if the target protein is a Transcription factor - changes expression of another protein, the response is slower.

Signal Inactivation

If a signaling molecule or receptor becomes active, there is always a way afterwards to inactivate it - such signal inactivation limits the cell’s response in both time and space - not overreact to a particular massage.

15b Extracellular Signals

Cell’s response to an extracellular signal depends on:

- Receptors & target proteins already present in the cell;

- Other signals received by the cell at the same time.

Extracellular Signaling molecules are often, but not always, small and diffusible.

The same signal can have different effects on different cell / receptor types:

Acetylcholine, a neurotransmitter:

- Binds to M2 muscarinic receptor, causing the decrease in heart rate;

- Stimulates muscarinic receptor, triggers the secretion of serous saliva;

- Binds to a different receptor protein (AChRs) on the muscle surface.

Classification

A. Extracellular Signals can be classified by how far they travel

[1] Hormones

- Extracellular signaling molecule that travels the farthest;

- Hormone is a regulatory substance produced in an organism and transported in tissue fluids such as blood or sap to stimulate specific cells or tissues into action.

- Hormones are used to coordinate responses across the body as a whole; they are Public Signals that many cells can respond to them.

[2] Local Mediators

- Local Mediators are Public Signals that many cells can respond to;

- They coordinate responses within a particular tissue;

- Local Mediators can travel via / diffuse through extracellular fluid and only affect nearby cells.

[3] Neurotransmitters

- Neurotransmitter is a chemical substance that is released at the end of a nerve fiber by the arrival of a nerve impulse and, by diffusing across the synapse or junction, causes the transfer of the impulse to another nerve fiber, a muscle fiber, or some other structure. Neurotransmitter can travel across synapse.

- Neurotransmitters are Private Signals, only one cell hears the message;

[4] Contact-Dependent Signaling

- Also known as juxtacrine signaling. It is a type of cell-cell or cell-extracellular matrix signaling in multicellular organisms that requires close contact.

- Contact-Dependent Signals do not travel; they are Private Signals and only one cell hears the message.

There are three types of juxtacrine signaling:

- A membrane ligand (protein, oligosaccharide, lipid) and a membrane protein of two adjacent cells interact.

- A communicating junction links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules.

- An extracellular matrix glycoprotein and a membrane protein interact.

Contact-dependent signals in development

Contact-dependent signaling is often used during development when an egg turns into a whole embryo.

Example: Formation of the epidermis:

- The epidermis includes both the skin and nerve cells - two neurons never develop right next to each other - the blue cell in the right picture expresses red membrane molecules on the surface - orange nerve cells directly next to the blue cell sense the red signal by using the green receptor - inhibit orange cells to become a blue nerve cell.