lec 4: Cell Communications and signaling I

molecular biology

The body’s natural response to danger

Fight or flight

Your brain detects the stressful situation and stimulate the release of stress hormones like

Adrenaline or epinephrine and cortisol

Adrenaline or epinephrine are from the …….. glands

Adrenal

Adrenaline and cortisol act on different parts of the body through

Cell signalling and communication pathways

As a result of the ……………. moleculles your body undergoes ……….. changes

signalling molecules, physiological

Physiology changes of fight or flight

include increased heart rate, heightened alertness, and energy mobilization. , clearer thinking, iquickened breathing

The human body relies on a complex system of communication between cells to

coordinate physiological responses and maintain homeostasis.

Homeostasis

regulation of the internal environment within the body

cell to cell communications

The process by which cells send and receive signals from each other to regulate various physiological functions.

Importance of cell to cell signalling

Essential response to changes in internal and external environment and many body functions, including:

1. Growth and development

2. repair

3. metabolism

4. immune functions

Dysfunction in cell communication leads to

various diseases including:

1. Cardiovascular disease

2. Neurological disorders

3. Cancer

4. Autoimmune Diseases

5. Endocrine Disorders

How do cell cell com work

Sender cells: cells communicate with each other using chemical messengers released from sender cells (e.g., small molecules, hormones, neurotransmitters,..etc)

Receiver cells: these messages binds to receptors on the surface of other receiver (target) cells.

Response: this binding triggers a series of events inside the cells that ultimately leads to a cellular response.

Types of communication

A. Local communication: neighboring cells

B. Long distance : at a distance from original signal

Local communication

1. Direct Contact

2. Autocrine and paracrine

3. Synaptic

Direct Contact

1. cell junctions

2. Contact dependent signals

Cell Junctions

1. Gap Junctions

2. Tight Junctions

3. Adheren Junction

4. Desmosomes

Gap Junctions

Made of transmembrane connexin proteins, link the cytoplasm of 2 cells together to exchange: ions, secondary messengers, and small metabolites

Allow the passage of calcium ion in mycardial cells, transmitting action potential across the entire heart causing heartbeats.

Tight junctions

Watertight seal, prevent molecules and watwr from passing between cells (bladder and intestines)

Adheren Junctions

Mediate cell to cell adhesion in intracellular signalling (endothelial cells)

Desmosomes

Link the cytoskeleton, allow the passage of water and ions between cells (skin)

Contact dependant signals

Surface protein moleculaes of one cell membrane, bind to surface receptor molecules on another cell as cell-cell recognition (immune cells). When the integral membrane protein binds to its receptor on adjacent cell, it elicit different responses

Synaptic Signaling

1. electrical signals along the axon of neurons

2. Neurotransmitters: from neurons into synapse and difuse to target cells that expresss a specific receptor.

Autocrine and Paracrine

Autocrine signals: when secreted protein molecules acts on the receptor of the same cells

Paracrine signals: when secreted protein molecules acts on the receptor of neighboring cells

Autocrine and paracrine signals (local regulators) diffuse to targets through interstitial fluid

Wound healing process

Damaged cells release chemical messengers called cytokines, ex: IL1, IL6, and TNF-alpha CAUSING:

1. inflammation: By recruiting immune cells to fight infection and clean dead cells

2. Cell proliferation: Growth factors such as PDGF, EGF, FGF, stimulate growth and division of cells at the wound site.

3. Angiogenesis: VEGF growth of new blood vessels to deliver oxygen and nutrients to healing cells

Long distance communication

1. Endocrine system

2. Nervous System

Endocrine system

Hormones/ Chemicals by endocrine cells to be circulated in the blood, to cells with specific receptors to respond to signal

Auto/Paracrine are in ………. vs Endocrine are in ………….

Interstitial fluids, blood

Nervous system

neurohormones, for action of distant target cells

Corticotropin-releasing hormone (CRH) is produced by the hypothalamus in the brain and stimulates the adrenal glands, above the kidneys, to produce and release cortisol, which is a stress hormone and plays a role in the body's response to stress.

Exosomes

Membrane-bound vesicles released from cell contain various molecules including proteins, nucleic acids and lipids.

Exosomes are also involved in cell-cell communication either through ……………communication or ……………… communication.

Autocrine/ Paracrine or long distance

Importance of exosomes

play an important role in many physiological and pathological processes (such as cancer, neurodegenerative diseases, cardiovascular diseases…etc).

Exosomes in Cancer

Transfer oncogenes and growth factors to promote tumor growth and metastsis

Molecular techniques to investigate cell communications

1. levels of specific genes or proteins

2. Co-culture experiments:

3. Scrape Loading adn Dye transfer

4. Live-cell imaging

Levels of specific genes or proteins

ex: connexin thro: qPCR for gene expression and western blot, ummunohistochemistry (flurorscence based), ir ELISA for protein level

Co-culturing experiments

different cell types are cultured together, and the effects of direct cell-to-cell communication and paracrine communication can be assessed.

one cell type may release a signaling molecule that can be tracked by a fluorescent dye, or secreted soluble paracrine molecules can be detected by ELISA

Scrape loading and dye transfer

assess the gap junction direct communication between adjacent cell, by inducing a scratch in cell, then incorporating fluorescent dye with molecular weight suitable to pass through gap junctions.

Live cell imaging

Monitor the real-time behavior of cells in response to direct and paracrine signals using live-cell imaging techniques

Signal Transduction pathway

converts a signal on a cell’s surface into a cellular response involved a series of steps that are collectively called signal transduction pathway

Cell signaling steps

1. reception

2. signal transduction

3. response

Reception

signal molecule a.k.a ligand attach to receptor on target cell, the receptor becomes activated, conformational changes happen and activate intracellular signal molecules

Transduction

Convert signal to response, could be a single step or multiple ones in a sequence of changes of different molecules.

relay molecules become activated and start a series of reactions or a cascade in the cytoplasm, might amplify signals

Response

final molecule in the signal transduction pathway will lead to a nuclear response and/or a cytoplasmic response within the cell.

(Eg: Regulate gene expression in the nucleus, activate an enzyme to catalyze a specific chemical reaction (for example, glycogen phosphorylase, as a response to fight-flight status)

T or F most cells combine intracellular and intercellular signalling

True

Intracellular

Inside the cell

Intercellular

Between cells

scientific research

1. describe a question or problem

2. propose hypothesis

3. test

4. form conclusions

5. communicate

side effects of radiotherapy

Radiation-induced cardiovascular diseases, especially atherosclerosis (10-15 years after Radiotherapy)

process of drug development

1. understand molecular mechanisms

2. identify potential targets

3. develop drugs

……………….. is the first event of atheroscelerosis

Endithelial cell dysfunction