Cell Communication By Balaji Krishnan

Learning Objectives

Exchange of mating factors Receptor  factor a factor Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell a a a/    The yeast, Saccharomyces cerevisiae, have two mating types, a and  Cells of different mating types locate each other via secreted factors specific to each type A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Signal transduction pathways convert signals on a cell’s surface into cellular responses

Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions (b) Cell-cell recognition

Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid. (a) Paracrine signaling (b) Synaptic signaling Electrical signal along nerve cell triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Target cell is stimulated.

Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling

Which of the following best describes a signal transduction pathway? 1.binding of a signal molecule to a cell protein 2.catalysis mediated by an enzyme 3.sequence of changes in a series of molecules resulting in a response 4.binding of a ligand on one side of a membrane that results in a change on the other side 5.the cell’s detection of a chemical or mechanical stimulus

The Three Stages of Cell Signaling Earl W. Sutherland suggested that cells receiving signals went through three processes –Reception –Transduction –Response A movie showing the three steps - 9wLEMTwA movie showing the three steps

Plasma membrane EXTRACELLULAR FLUID CYTOPLASM ReceptionTransduction Response Receptor Signaling molecule Activation of cellular response Relay molecules in a signal transduction pathway Where would you place epinephrine, cyclic AMP and Glucose from the movie that you saw? Which would be reception, transduction and response EACH STUDENT - Place the following correctly in the above box: Reception, Transduction, Response, Receptor, Signaling Molecule, Activation of cellular response, Extracellular fluid, Cytoplasm, Relay Molecules

Receptors in the Plasma Membrane Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane There are three main types of membrane receptors –G protein-coupled receptors –Receptor tyrosine kinases –Ion channel receptors

G-protein-coupled receptor (GPCRs) are the largest family of cell-surface receptors A GPCR is a plasma membrane receptor that works with the help of a G protein The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Protein/index.htmlhttp://entochem.tamu.edu/G- Protein/index.html

Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Abnormal functioning of RTKs is associated with many types of cancers

A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na + or Ca 2+, through a channel in the receptor hill.com/sites/ /student_view0/chapter2/ animation__receptors_linked_to_a_channel_protein.html hill.com/sites/ /student_view0/chapter2/ animation__receptors_linked_to_a_channel_protein.html

Receptor Signaling molecule Activated relay molecule Phosphorylation cascade Inactive protein kinase 1 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein Cellular response ATP ADP ATP ADP ATP ADP PP P P P P i

In reactions mediated by protein kinases, what does phosphorylation of successive proteins do to drive the reaction? 1.make functional ATP 2.change a protein from its inactive to its active form 3.change a protein from its active to its inactive form 4.alter the permeability of the cell’s membranes 5.produce an increase in the cell’s store of inorganic phosphates

Small Molecules and Ions as Second Messengers The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger” Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by GPCRs and RTKs Cyclic AMP and calcium ions are common second messengers

Which of the following is an example of signal amplification? 1.catalysis of many cAMP molecules by several simultaneously binding signal molecules 2.activation of 100 molecules by a single signal binding event 3.activation of a specific gene by a growth factor 4.activation of an enzyme molecule 5.utilization of a second messenger system

Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Adenylyl cyclase Phosphodiesterase Pyrophosphate AMP H2OH2O ATP P i P cAMP

Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases cAMP usually activates protein kinase A, which phosphorylates various other proteins Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase

Calcium Ions and Inositol Triphosphate (IP 3 ) Calcium ions (Ca 2+ ) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Pathways leading to the release of calcium involve inositol triphosphate (IP 3 ) and diacylglycerol (DAG) as additional second messengers

Mitochondrion EXTRACELLULAR FLUID Plasma membrane Ca 2  pump Nucleus CYTOSOL Ca 2  pump Endoplasmic reticulum (ER) ATP Low [Ca 2  ] High [Ca 2  ] Key

G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Cellular responses Ca 2  (second messenger) Ca 2  GTP

A steroid hormone binds to an intracellular receptor. When it does, the resulting complex is able to do which of the following? Why? – open channels in the membrane for other substances to enter – open channels in the nuclear envelope for cytoplasmic molecules to enter – mediate the transfer of phosphate groups to/from ATP – act as a transcription factor in the nucleus – make water-soluble molecules able to diffuse across membranes

Growth factor Receptor Reception Transduction CYTOPLASM Response Inactive transcription factor Active transcription factor DNA NUCLEUS mRNA Gene Phosphorylation cascade P

Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2Response 3 Response 4 Response 5 Activation or inhibition Cell B. Pathway branches, leading to two responses. Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

Mitochondrion Ced-9 protein (active) inhibits Ced-4 activity Receptor for death- signaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Death- signaling molecule Ced-9 (inactive) Cell forms blebs Active Ced-4 Active Ced-3 Other proteases Nucleases Activation cascade (b) Death signal

One of the important outcomes of apoptosis is protection of neighboring cells. Which of the following is responsible? 1.cell shrinkage and blebbing 2.destruction of the cell’s DNA 3.formation of numerous vesicles to be digested 4.action of tyrosine kinases 5.activation of specific proteins

Apoptotic Pathways and the Signals That Trigger Them 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 evolved early in animal evolution and is essential for the development and maintenance of all animals Apoptosis may be involved in some diseases (for example, Parkinson’s and Alzheimer’s); interference with apoptosis may contribute to some cancers

Interdigital tissue Cells undergoing apoptosis Space between digits 1 mm