1. Cell Communication

2. Overview: The Cellular Internet Cell-to-cell communication is absolutely essential for multicellular organisms Nerve cells must communicate pain signals to muscle cells (stimulus) in order for muscle cells to initiate a response to pain

3. Biologists have discovered some universal mechanisms of cellular regulation

4. External Signals Signal Transduction Pathway

5. Yeast cells identify their mates by cell signaling (early evidence of signaling)  factor Receptor Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 1 Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. New a/  cell. The nucleus of the fused cell includes all the genes from the a and a cells. 2 3  factor Yeast cell, mating type a Yeast cell, mating type    a/  a a

6. Signal Transduction Pathways  Convert signals on a cell’s surface into cellular responses  Are similar in microbes and mammals suggesting an early, and common, origin.

7. Cells in a multicellular organism (tissues, organs, systems) communicate via chemical messengers Sometimes cells need to send messages to itself (autocrine signaling). Messages need to be sent both shorter distances (paracrine signaling), as well as longer distances (endocrine signaling). Local and Long-Distance Signaling

8. Animal and plant cells  Have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

9. Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. In local signaling, animal cells  May communicate via direct contact

10. In other cases, animal cells communicate using local regulators (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Target cell is stimulated Local signaling

11. 11 A hormone is a chemical released by a cell in one part of the body, that sends out messages that affect cells in other parts of the organism All multicellular organisms produce hormones plant hormones are also called phytohormones Hormones in animals are often transported in the blood Long-Distance Signaling Long-Distance Signaling Endocrine signaling

12. In long-distance signaling  Both plants and animals use hormones (e.g. in animals-insulin, in plants-auxin) Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Long-distance signaling Blood vessel Target cell Endocrine cell Figure 11.4 C

13. Earl W. Sutherland  Discovered how the hormone epinephrine acts on cells, stimulating the breakdown of glycogen in the liver and skeletal muscle cells The Three Stages of Cell Signaling

14. Sutherland’s Three Steps Sutherland suggested cells that are receiving signals went through three processes: Reception Transduction Response

15. EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Figure 11.5 Overview of basic cell signaling Reception 1 Transduction 2 Response 3

16. Step One - Reception Reception occurs when a signal molecule binds to a receptor protein, causing it to change shape Receptor proteins are on the cell’s surface.

17. The binding between signal molecule (ligand) and receptor is highly specific A conformational change in a receptor is often the initial transduction of the signal.

18. Step Two - Transduction The binding of the signal molecule alters the receptor protein in some way The signal usually starts a signaling cascade, a series of enzyme catalyzed reactions, known as a signal transduction pathway Multi-step pathways can amplify a signal

19. Step Three - Response Cell signaling leads to regulation of cytoplasmic activities or initiation of transcription Signaling pathways regulate a variety of cellular activities

20. Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein DNA mRNA NUCLEUS CYTOPLASM Plasma membrane Hormone- receptor complex New protein Figure 11.6 Example of Pathway Steroid hormones bind to intracellular receptors 1 The steroid hormone testosterone passes through the plasma membrane. The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5 Testosterone binds to a receptor protein in the cytoplasm, activating it. 2 The hormone- receptor complex enters the nucleus and binds to specific genes. 3

21. Other pathways regulate genes by activating transcription factors that turn genes on or off Reception Transduction Response mRNA NUCLEUS Gene P Active transcription factor Inactive transcription factor DNA Phosphorylation cascade CYTOPLASM Receptor Growth factor Figure 11.14

22. Signal response is terminated quickly by the reversal of ligand binding Termination of the Signal

23. There are three main types of membrane receptors:  G-protein-linked  Tyrosine kinases  Ion channel Receptors in the Plasma Membrane

24. G-Protein-Coupled Receptors G-protein-linked Receptor Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated Receptor Signal molecule Inactivate enzyme Segment that interacts with G proteins GDP GTP P iP i Signal-binding site Figure 11.7 GDP GPCR receives signal GPCR activates G-protein by exchanging a GTP for a GDP G protein binds to an effector protein Effector protein initiates response – production of 2 nd messengers [Ca 2++, cAMP, for example] GPCR signaling is deactivated when GTP is hydrolyzed GTP  GDP + P i GPCR receives signal GPCR activates G-protein by exchanging a GTP for a GDP G protein binds to an effector protein Effector protein initiates response – production of 2 nd messengers [Ca 2++, cAMP, for example] GPCR signaling is deactivated when GTP is hydrolyzed GTP  GDP + P i

25. 25 Some examples of systems using G-linked receptors include: yeast mating, epinephrine, neurotransmitters “different proteins are receptors for different neurotransmitters…” Acetylcholine is commonly secreted at neuromuscular junctions, the gaps between neurons and muscle cells, where it stimulates muscles to contract. At OTHER junctions, it may produce an inhibitory post-synaptic response.

26. 26 Enzymes, like cholinesterase degrade neurotransmitters. The degraded neurotransmitters are then rapidly recycled, and taken up by the pre-synaptic cell.

27. Receptor tyrosine kinases Signal molecule Signal-binding site CYTOPLASM Tyrosines Signal molecule  Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P P P P P P Tyr P P P P P P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) 6 ATP 6 ADP Figure 11.7

28. 28 Some examples of signaling pathways that employ tyrosine kinase receptors include: transformation of glucose to glycogen glucose export, and activation of transcription factors promoting cell growth and differentiation Ability of tyrosine kinase receptors to amplify the original signal is an important difference between tyrosine kinase and G-coupled proteins Ability of tyrosine kinase receptors to amplify the original signal is an important difference between tyrosine kinase and G-coupled proteins

29. Ion channel receptors Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Figure 11.7 Gate closed Ions

30. Some examples of signaling pathways that employ gated ion channel receptors include: Nerve impulses Muscle contraction [due to sodium &/or potassium gates opening or closing]