Lecture 2 - Cellular signalling intro

Why do cells need to communicate in different ways?

Multicellular organisms have many cell types, to function as a whole these specialised cells must function together and that requires coordination.

Cells group together into tissues and organs, and the cells need to exchange information to respond to changes within the organ, or elsewhere in the organism. This communication can occur through various signaling methods, including chemical signals, electrical signals, and direct contact between cells.

Organisms need to detect and respond to stimuli;

• sounds, smells, tastes etc need to be transduced,

• genes need to be switched on and off

• metabolites need to be released or taken up

• other cells need to be recruited for wounds and infections

• metabolic states - maintain homeostasis, fluid level, temperature, digestion.

Signals can tell a cell to:

• Stay alive

• Grow and divide, replicate

• Differentiate to become a specialised cell

• Die

Define: Direct vs Indirect signalling

Direct signalling is upclose, it requies membrane to membrane contact. Signalling cell has a membrane bound signalling molecule, and the target cell has a membrane bound receptor molecule. Indirect signalling involves the release of signaling molecules into the extracellular space, allowing them to travel to and interact with target cells at a distance, often through the bloodstream.

Direct cellular communication

Includes contact inhibition, where cells grow until the contact each other, and then stop growing.

When this occurs, gap junctions form where the cells meet, and create an aqeous channel to allow the passage of small molecules and ions, but not large proteins or DNA. This allows constant communication of each cells current state.

Another form of direct communication occurs when cells containing complementary ligands and receptors bound to the surface of their membranes come together, and bind to one another. This can occur in immune responses, immune cells use cell surface markers to differentiate between “self” cells and other things like cells infected by pathogens, pathogens themselves, and phagocytes that have already englufed an infected cell.

Define: Second messenger principle

Indirect signalling, where a primary signalling molecule binds to a receptor which results in LICC, triggers secondary signalling molecules to be produced inside the target.

Define: Receptor & Ligand

Ligands are produced by signalling cells (effector cells), and then released. They travel via blood or ECF to the target cell. They are also known as primary signalling molecules.

Receptors recognise and bind ligands causing LICC, they are on the surface of the target cell, and this binding activates intracellular production of secondary signalling molecules.

What does LICC stand for, and what does it mean?

Ligand Induced Conformational Change.
This occurs when a ligand binds to a receptor, and the conformational change causes an action within the cell that leads to secondary messengers being created/activated.

Define: Endocrine & Paracrine

Endocrine and paracrine signalling both involve the release of ligands.

Endocrine signalling involves ligands travelling through the blood or ECF to reach target cells at a distance.

Paracrine signaling involves paracrine hormones being released and, instead of entering the blood, diffuse through the tissue to target cells withing the organ.

Define: Agnoist and Antagonist

Agonists and antagonists both bind to receptors. While Ligands are physiologically native, and they produce a natural response in the target, agonists and antagonists are

Define: Synaptic signalling

Indirect signalling, but over a small space known as the synaptic cleft.

Neurons contain a body with the nucleus, and the axon and dendrites are long protrusions from this body.

The axon is very long, allowing signals to be transmitted over long distances. Dendrites recieve the signals, and are numerous to make this more efficient.

The axon terminals (generally?) contain presynaptic terminals containing neurotransmitters, when voltage gates channels open, these are released into the synaptic cleft and diffuse across to the postsynaptic membrane of the recieving cell.

When the recieving cell bind enough neurotransmitters, the action potential triggered can send the electrical signal a long distance.

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What is the structure and function of gap junctions?

What are the three principle types of indirect signalling?

Membrane bound receptors linked to:

• G-proteins

• Catalytic activity

• Ion channels

What are the principle types of primary signalling molecules (ligands)?

Hormones

Local mediators

Neurotransmittters

How does the target cell recognise external signals?

Signal ligands bind to their receptors, either on the outer membrane, or in the cytoplasm.

Binding can induce changes, conformational changes can induce changes in other mols, redistribute charge, activate/inactivate catalytic sites, expose sites etc.

What are molecular switches ?

Generic methods of molecular switching: Phosphorylation, de-phosphorylation, and GTP binding proteins.

Cellular activity changes triggered by switching on or off a pathway or protein.

Describe: Phosphorylation and de-phosphorylation

Enzymes can add phosphate groups to amino acids, these are termed Kinase enzymes. Conversely, enzymes that remove phosphate groups are known as Phosphatases.

Phosphorylation usually switches on, or activates, a protein, but can also inhibit enzyme actions or deactivate them.

Describe GTP binding and hydrolysis

GTP (guanosine triphosphate) can be bound by proteins in order to “activate” them. These are classed as GTP-binding proteins.

GTP can be hydrolsed to GDP to deactivate them, usually catalysed by the GTP binding protein itself via intrinsic GTPase activity.

Regulatory proteins control this binding activity. GEF (Guanine exchange factor) causes the exchange of GDP for GTP, and GAP (GTPase activating proteins) cause more rapid hydrolysis of GTP to GDP.

GAP and GEF are analagous to Kinases and phosphatases in phosphorylation.