Cells communicate by generating transmitting and receiving chemical

Cells communicate by generating, transmitting and receiving chemical signals SIGNAL TRANSDUCTION PATHWAYS LINK SIGNAL RECEPTION WITH CELLULAR RESPONSE

Cascade of Molecular Interactions � Relay molecules – often proteins, transmit the signal from the receptor to the final cellular response � Message is sent by phosphorylating and dephosphorylating protiens (results in shape changes) � Phosphorylation done by kinases – activating � Dephosphorylation done by phophatases - deactivating Phosphorylation Cascade

Cascade of Molecular Interactions �Second messengers – water soluble molecules and / or ions can be involved in the transduction of messages from signal to cellular response �Second messengers are often essential to the function of cascade �Small / water soluble = rapid diffusion thru cells

Illustrative Example: cyclic AMP (c. AMP) as a second messenger � First messenger (i. e. epinephrine) triggers G-protein receptors � Receptor protein triggers adenylyl cyclase which catalyses Rapid synthesis of many c. AMP molecules from Atp molecules � High camp concentrations are quickly reduced by phosphodiesterase (which converts c. AMP to AMP) � Repeated stimulation by first messenger is required to maintain high concentrations of camp in cytoplasm � High levels of c. AMP trigger the activation of kinases that eventually bring about the cellular response

Illustrative Example: calcium (Ca 2+) ions and inositol triphosphate (IP 3 ) as a second messengers � Calcium is more widely used than c. AMP as a second messenger � Ca 2+ used with G-protein receptors and tyrosine kinase pathways � Good secondary messenger because the concentration of Ca 2+ is usually very low (it is actively pumped out of cytoplasm either into extra cellular fluid, into ER, or into mitochondria) � IP 3 is another secondary messenger which can stimulate the release of Ca 2+

Cellular Response �Nuclear Responses Many signaling pathways regulate protein synthesis by turning a gene on or off Phosphorylation cascades can end by activating or inactivating a transcription factor

Cellular Response �Cytoplasmic Response Signaling pathways regulate the activity of proteins found in the cytosol For example: Epinephrine stimulating the breakdown of glycogen via signal transduction

Signaling molecule Specificity of cell signaling The particular protiens a cell possesses determine what signaling molecules it responds to and the nature of the response. 4 different cells each respond to the same signaling molecule in a different way Receptor Relay molecules Response 1 Response 2 Cell A. Pathway leads to a single response. Response 3 Cell B. Pathway branches, leading to two responses. Activation or inhibition Response 4 Cell C. Cross-talk occurs between two pathways. Response 5 Cell D. Different receptor leads to a different response.

Apoptosis integrates multiple cell-signaling pathways �Apoptosis – programmed cell death; cellular agents chop up the DNA, fragment the organelles & other cellular components; the cell shrinks and becomes lobed (blebbing); cell parts are packaged up in vesicles that are engulfed & digested by specialized scavenger cells

Apoptosis controlled by signal transduction pathways �Study of soil worm (Caenorhabditis elegan) reveal that there are cell death genes and cell death proteins (Ced -3 and Ced-4) that are always present in the cell in the inactive form. �These proteins can be “turned on or off” by signal transduction pathways that Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Ced-4 Receptor for deathsignaling molecule Ced-3 Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Deathsignaling molecule Active Ced-4 Ced-3 Activation cascade (b) Death signal Other proteases Nucleases

Apoptosis �Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis �Apoptosis can be triggered by: An extracellular death-signaling ligand DNA damage in the nucleus Protein misfolding in the endoplasmic reticulum �Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers

Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals Interdigital tissue 1 mm