2E2 – Timing and coordination of physiological events are regulated by multiple mechanisms. 3B2 – A variety of intercellular and intracellular signal transmissions mediate gene expression. 3D – Cells communicate by generating, transmitting, and receiving chemical signals. 1 – Cell communication processes share common features that reflect a shared evolutionary history. 2 – Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling. 3 – Signal transduction pathways link signal reception with cellular response. 4 – Changes in signal transduction pathways can alter cellular response.

Chapter 11~ Cell Communication

Signal-transduction pathway I Def: Process by which a signal on a cell’s surface is converted into a specific cellular response Local signaling (short distance): Messenger moleucles are secreted and travel short distances Paracrine signaling (growth factors) Single cell produces factors that are received and responded to by numerous cells simultaneously Synaptic (neurotransmitters) Electrical signal stimlates secretion of chem signal which moves across the synapse to another cell

Signal-transduction pathway II Long distance: hormones Animals - aka endocrine signaling Hormones released into circulatory system to travel to target cells Nervous system – signal continues along a series of cells Plants – growth regulators Travel by vessels, diffusion through cells, or the air as a gas

Stages of cell signaling Discovered by Earl Sutherland (‘71) Glycogen depolymerization by epinephrine 3 steps: (1) Reception: target cell detection (2) Transduction: single-step or series of changes (3) Response: triggering of a specific cellular response

Reception I A signal molecule binds to a receptor protein and causes a conformation change Ligand – molecule that specifically binds to another Compare to a key in a lock – similar to enzymes Intracellular receptors Proteins found in cytoplasm or nucleus of target cell Messenger must pass through plasma membrane Must be hydrophobic or small enough Ex. Steroids, thyroid hormones Testosterone – released by testis Target cells have receptor in nucleus Binds w/ protein activating it Active form enters nucleus and turns on specific genes

Reception II Plasma membrane receptors (pg 206-208) Water soluble signal molecules Receptor transmits info by changing shape 3 main types (1) G-protein-linked receptors Receptor is made of 7 transmembrane α helices Works w/ the help of a G protein which is just inside the membrane Is on or off depending on which of 2 guanine nucleotides is attached (GDP or GTP) Signal molecule binds to receptor and changes its shape Binds to GDP causes GTP to replace it GTP binds to an enzyme and activates it Reverts to GDP

Reception III (2) Receptor Tyrosine Kinases Can trigger simultaneous signal transduction pathways Regulates cell growth and reproduction Malfunction may lead to cancer Kinase – enzyme catalyzes phosphate transfers in cytoplasm Portion of receptor acts as a tyrosine kinase Signal molecule causes 2 receptors to move close together (dimerization) Activates tyrosine kinase Attaches phosphates to tyrosines Different inactive proteins bind to phosphorylated tyrosine and become activated

Reception IV (3) Ligand-gated ion channels Important for nervous system When receptor changes shape a “gate” opens/closes allowing ions through or blocking flow Cause changes in Na+ and Ca- concentration levels

Transduction I Series (cascade) of molecular interactions relay signals from receptors to target molecules Begins when receptor changes Relay molecules = proteins @ each step info is transduced into a different form Usually a conformation change in protein Caused by phosphorylation

Transduction II Protein kinase – enzyme that transfers a phosphate from ATP to protein – many different kinds Addition of phosphate activates protein Dephosphorylation – removal of phosphate Inactivates proteins – turn off pathway Caused by enzymes called protein phosphatases

Second Messengers I Small molecules and ions that are not proteins 1st is the extracellular signal molecule that binds to membrane Are able to diffuse through cells 2 most common:cyclic AMP &calcium ions

Second Messengers II (1) cyclic AMP (cAMP) Adenylyl cyclase (enzyme in membrane) converts ATP to cAMP Concen. increases and spreads through cell Only lasts while signal molecule is attached Concen. decreases because phosphodiesterase changes cAMP back to ATP

Second Messengers III (2)Calcium ions and Inositol Triphosphate (IP3) Ca concen. increases triggered by other secondary messengers Phospholipid in membrane is broken into IP3 and diaglycerol (DAG) IP3 goes on to stimulate Ca increase

Response Regulation of cellular activities In cytoplasm Ex. Open/close ion channel; change in metabolism May cause synthesis of enzymes

Specificity of Cell Signaling Get different results from different cells because they have different collections of proteins Ex. Epinephrine – a liver cell breaks down glycogen; heart cells contract for faster heart beat

Signaling Efficiency Scaffolding proteins – large relay proteins w/ other relay proteins attached Increases efficiency