Cell Communication Chapter 11 Local regulators – in the vicinity a.Paracrine signaling – nearby Cells are acted on by signaling Cell (ie. Growth factor) b. Synaptic signaling-neurotrans- mitters cross the synapse (gap) Between nerve cell and target

Long Distance Signaling Hormones – Endocrine signaling – Plant growth regulators

Figure 11.4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions (b) Cell-cell recognition

Figure 11.5 Local signaling Long-distance 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. Endocrine cell Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling

The Three Stages of Cell Signaling: A Preview – Reception – Transduction – Response © 2011 Pearson Education, Inc.

Receptors in the Plasma Membrane There are three main types of membrane receptors – G protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors © 2011 Pearson Education, Inc.

ligand-gated ion channel receptor acts as a gate when the receptor changes shape 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 © 2011 Pearson Education, Inc.

Figure 11.7d Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed

G-protein-coupled receptor (GPCRs 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 © 2011 Pearson Education, Inc.

Figure 11.7b G protein-coupled receptor Plasma membrane G protein (inactive) CYTOPLASM Enzyme Activated receptor Signaling molecule Inactive enzyme Activated enzyme Cellular response GDP GTP GDP GTP P i GDP

Receptor tyrosine kinases (RTKs) membrane receptors that attach phosphates to tyrosines can trigger multiple signal transduction pathways at once Abnormal functioning of RTKs is associated with many types of cancers © 2011 Pearson Education, Inc.

Figure 11.7c Signaling molecule (ligand) Ligand-binding site  helix in the membrane Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Signaling molecule Dimer Tyr P P P P P P P P P P P P Activated tyrosine kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine kinase (phosphorylated dimer) Activated relay proteins Cellular response 1 Cellular response 2 Inactive relay proteins 6 ATP 6 ADP

Intracellular Receptors found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes © 2011 Pearson Education, Inc.

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 © 2011 Pearson Education, Inc.

Figure 11.7d Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed

Intracellular Receptors found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes © 2011 Pearson Education, Inc.

Figure Hormone (testosterone) Receptor protein Plasma membrane EXTRACELLULAR FLUID Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM New protein

Signal Transduction Pathways mostly proteins Produces a domino affect At each step, the signal is transduced into a different form, usually a shape change in a protein © 2011 Pearson Education, Inc.

Protein Phosphorylation and Dephosphorylation Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation © 2011 Pearson Education, Inc.

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 Figure 11.10

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 ATP ADP ATP ADP ATP ADP PP P P P i P Figure 11.10a

Cyclic AMP Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Cholera – regulating G protein for salt and water secretion. No GTP to GDP stimulates more cAMP cGMP – relaxes smooth muscles – effects of viagra © 2011 Pearson Education, Inc.

Figure Adenylyl cyclase Phosphodiesterase Pyrophosphate AMP H2OH2O ATP P i P cAMP

Calcium Ions and Inositol Triphosphate (IP 3 ) Calcium is an important second messenger because cells can regulate its concentration Lower in cytosol than extracellular (10,000x) Active transport of Ca++ out or from cytosol to ER and mitochondria (IP 3 and DAG) © 2011 Pearson Education, Inc.

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

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 © 2011 Pearson Education, Inc. Animation: Signal Transduction Pathways

Nuclear and Cytoplasmic Responses regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule in the signaling pathway may function as a transcription factor © 2011 Pearson Education, Inc.

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

Fine-Tuning of the Response There are four aspects of fine-tuning to consider – Amplifying the signal (and thus the response) – Specificity of the response (liver/heart) – Overall efficiency of response, enhanced by scaffolding proteins (brain) – Termination of the signal © 2011 Pearson Education, Inc.

Figure 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.

Figure Signaling molecule Receptor Plasma membrane Scaffolding protein Three different protein kinases

Concept 11.5: Apoptosis integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells © 2011 Pearson Education, Inc.

Figure  m

Apoptotic Pathways and the Signals That Trigger Them Caspases - the main proteases that carry out apoptosis triggered by – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum © 2011 Pearson Education, Inc.