Lecture 9: Cell Communication Bio Sci 93

Cell communication

Essential for multicellular and unicellular organisms, because cells must communicate to coordinate their activities. Signaling mechanisms are highly conserved: the same types of signaling systems are used in all domains of life.

Quorum sensing

Example of cell-cell communication in unicellular microorganisms, shown in the marine bacterium Vibrio harveyi.

Yeast mating signaling

Example of cell-cell communication in a unicellular eukaryote, Saccharomyces cerevisiae. Yeast mating receptors are G-protein-coupled receptors (GPCRs).

Three-stage signaling pathway

Reception, transduction, and response. Together they make up a signal transduction pathway.

Reception

Stage 1: a signal (ligand) binds to a receptor. This occurs most of the time (but not always) at the cell surface. Binding induces a change in the location, shape, or activity of the receptor.

Transduction

Stage 2: relay molecules amplify the signal of a few signaling molecules, usually through second messengers and phosphorylation cascades. (Not on the midterm.)

Response

Stage 3: the readout of signal reception and transduction. Can include gene expression changes, cytoskeletal changes, differential localization of a protein, or a change in a protein's activity.

Ligand

The signal that binds to a receptor. Induces a change in the receptor's location, shape, or activity.

Hormone

Signaling molecule secreted by a cell that travels to target cells at distant sites. In animals it travels in the circulatory system. Example: insulin secreted from the pancreas.

The four types of signals

1) Secreted signals that act locally. 2) Secreted signals that act at distant sites. 3) Intercellular signals. 4) Cell surface signals.

Intercellular signals

Important in adjacent tissue cells. Example: Ca2+ signaling that produces a coordinated muscle contraction in a tissue.

Cell surface signals

Important during development and for the immune response. Example: B cells secrete antibodies that bind to bacterial cells, and white blood cells recognize the antibody on the bacterium's surface and phagocytose it.

Paracrine signaling

Secreted signals that act locally (e.g., growth factors). Example: PDGF released from aggregating platelets stimulates wound healing.

Synaptic signaling

Type of local secreted signaling using neurotransmitters released by neurons. Example: dopamine release.

Endocrine signaling

Hormones are secreted and travel to distant target cells (in animals, through the circulatory system). Very specific, because only cells with receptors for the hormone can respond.

Receptor specificity

A signal can only cause a response in cells that have the right receptor, which is why hormones can travel throughout the body without affecting every cell.

Plasma membrane receptors

Membrane proteins that bind ligands that are secreted, hydrophilic (water soluble), or membrane-bound.

Intracellular receptors

Cytoplasmic or nuclear proteins that bind ligands that are hydrophobic (lipid soluble) and can cross the membrane.

Prevalence of cell-surface receptors

About 20% of all proteins encoded by the human genome are cell-surface receptors.

G-protein-coupled receptor (GPCR)

Cell-surface receptor (7 transmembrane domains). Ligands include photons, ions, odorants, hormones, and neurotransmitters. Examples: yeast mating receptors and dopamine receptors. More than 1000 GPCRs have been characterized in humans.

Kinase

Enzyme that catalyzes the transfer of phosphate groups to another molecule.

Receptor tyrosine kinase (RTK)

Cell-surface receptor that is a kinase. Forms a dimer when activated. One RTK can activate multiple downstream pathways. Often involved in cell growth and can be dysfunctional in cancer cells. Example: the insulin receptor.

RTKs and cancer treatment

Because RTKs can be dysfunctional in cancer cells, antibodies that block RTKs and drugs that block their action are used to treat different types of cancers.

Ligand-gated ion channel

Ion channel opened when a ligand (such as a neurotransmitter) binds. Ions such as Na+ or Ca2+ flow in or out of the cell, depending on the receptor. Important for communication between nerve cells.

Voltage-gated ion channel

Gated ion channel that is activated by electrical signals.

Stretch-activated ion channel

Gated ion channel that is activated by a mechanical change in the cell membrane.

Gated ion channels in organelles

Some gated ion channels are present in the membranes of organelles, for example the smooth ER.

Intracellular receptor ligands

Ligands that directly cross the membrane bilayer, such as steroid hormones (e.g., aldosterone), thyroid hormones, and nitric oxide (NO).

Intracellular receptor mechanism

The receptor is in the cytosol or nucleus. The hormone-receptor complex acts as a transcription factor, causing changes in gene expression.

Matching ligands to receptor types

Hydrophilic ligands (e.g., neurotransmitters, peptide hormones, growth factors) bind surface receptors (GPCR, RTK, gated ion channels). Hydrophobic ligands (steroid hormones, thyroid hormones, NO) bind intracellular receptors.

GPCR vs. RTK

GPCR: seven-transmembrane receptor with a very large family (more than 1000 in humans); ligands include hormones, neurotransmitters, odorants, and photons. RTK: receptor that is an enzyme (kinase), forms dimers, and is often linked to cell growth and cancer.

Relay molecules

Molecules in the transduction stage that amplify the signal. Usually involves second messengers and phosphorylation cascades.

Cellular response examples

Gene expression changes, cytoskeletal changes, differential localization of a protein, or a change in a protein's activity.