Unit 4 (Cell signal pathways)

Cell Communication

Cell-to-cell communication is critical for the function and survival of cells

• Responsible for the growth and development of multicellular organisms

How do cells communicate?

1. Direct contact

2. Local signaling

3. Long-distance signaling

Direct contact

• Communication through cell junctions

• Signaling substances and other material dissolved in the cytoplasm can pass freely between adjacent cells

• Animal cells: gap junctions

• Plant cells: plasmodesmata

Local regulators

• A secreting cell will release chemical messages (local regulators/ligands) that travel a short distance through the extracellular fluid.

• The chemical messages will cause a response in a target cell

• Ex. paracrine/synaptic signaling

Paracrine signaling

Secretory cells release local regulators (ie growth factors) via exocytosis to an adjacent cell.

Synaptic signaling

• Occurs in animal nervous systems

• Neurons secrete neurotransmitters, which diffuse across the synaptic cleft-space between the nerve cell and the target cell

Long-distance signaling

• Animals and plants use hormones for long-distance signaling

• Plants: release hormones that travel in the plant vascular tissue (xylem and phloem) or through the air to reach the target cell

• Animals: Use endocrine signaling - specialized cells release hormones into the circulatory system, where they reach target cells

Cell signaling overview

1. Reception: Ligand binds to receptor

2. Transduction: Signal is converted

3. Response: a cell process is altered

Stage 1: Reception

• The detection and reception of a ligand by a receptor in the target cell

• All receptors have an area that interacts with the ligand and an area that transmits a signal to another protein

• The binding between ligand and receptor is highly specific

• When the ligand binds to the receptor, the receptor activates via conformational change

• Allows the receptor to interact with other cellular molecules

• Initiates transduction signal

Receptor

A macromolecule that binds to a signal molecule (ligand)

• Can be in the plasma membrane or intracellualr

Plasma Membrane Receptors

• Most common type of receptor involved in signal pathways.

• Binds to ligands that are large, polar, and water soluble

• Examples: G protein coupled receptors (GPCRs) and ligand gated ion channels

Intracellular Receptors

• Found in the cytoplasm or nucleus of target cell

• Binds to ligands that can pass through the plasma membrane

• ie hydrophobic molecules (steroid and thyroid hormone and gasses like nitric acid)

Stage 2: Transduction

• The conversion of an extracellular signal to an intracellular signal that will bring about a cellular response

• Requires a sequence of changes in a series of molecules known as a signal transduction pathway

Signal transduction pathway

Regulates protein activity through:

• Phosphorylation by the enzyme protein kinase relays a signal inside the cell

• Dephosphorylation by the enzyme protein phosphatase shuts off pathways

• A change in shape means a change in function

• The ligand is being transduced

Second messangers

• During transduction, the signal is amplified

• Second messengers: small, non-protein molecules and ions help relay the message and amplify the response

• cyclic AMP (cAMP) is a common second messenger

• Adenine monophosphate (AMP): ATP lost 2 phosphates

Stage 3: Response

The first molecule in the signaling pathway converts the signal to a response that will alter a cellular response

• Examples:

1. Protein that can alter membrane permeability

2. Enzyme that will change a metabolic process

3. Protein that turns genes on or off

Signal transduction pathways (2)

• Can influence how a cell responds to its environment

• Can result in changes in gene expression and cell function, which can alter phenotypes or result in cell death (apoptosis)

Changes in signal transduction pathways

• Mutations to receptor proteins or any component of the signaling pathway will result in a change to the transduction of the signal.

Important receptors

• Eukaryotic organisms

1. G protein coupled receptors (GPCRs)

2. Ion channels

GPCRs

• G protein coupled receptors (GPCRs)

• Largest category of cell surface receptors

• Important in animal sensory systems

• Binds to a G protein that can bind to GTP (an energy molecule similar to ATP)