Cell Communication Ch. 11

1. Cell-to-cell communication is essential for multicellular organisms • cells send and receive chemical messages constantly to coordinate the actions of distant organs, tissues, and cells. • Cells can receive a message, transfer the information across the plasma membrane, and then produce changes within the cell in response to the message Cell Communication Ch. 11

2. Paracrine- occurs between local cells where the signals elicit quick responses and last only a short amount of time due to the degradation of ligands. Endocrine- occurs between distant cells and is mediated by hormones released from specific endocrine cells that travel to target cells, producing a slower, long-lasting response. Autocrine- signals are produced by signaling cells that can also bind to the ligand that is released, which means the signaling cell and the target cell can be the same or a similar cell. Direct signaling can occur by transferring signaling molecules across gap junctions between neighboring cells. Direct Types of Cell Signaling

3. Autocrine/Synaptic signaling respond to molecules they produce themselves. Examples include many growth factors. Local

4. 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

5. Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses acrosssynapse Secretory vesicle Local regulator diffuses through extracellular fluid Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. (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. In other cases, animal cells communicate using local regulators

6. Intracellular- are located in the cytoplasm of the cell and are activated by hydrophobic ligand molecules that can pass through the plasma membrane -nonpolar and fat soluble • Cell membrane- bind to an external ligand molecule and convert an extracellular signal into an intracellular signal. • Three general categories of cell-membrane receptors include: • Ion channel-linked- bind a ligand and open a channel through the membrane that allows specific ions to pass through. • G-protein-linked- bind a ligand and activate a membrane protein called a G-protein, which then interacts with either an ion channel or an enzyme in the membrane. • Receptor tyrosine kinase(Enzyme-linked)-are receptors with intracellular domains that are associated with an enzyme Types of Receptors

7. Gate closed Signalmolecule(ligand) Ions Ligand-gated ion channel receptor Plasma Membrane Gate open Cellularresponse Gate close Ion channel receptors

8. G-Protein-Coupled Receptor

9. Hydrophobic signaling molecules or ions(ligands) can diffuse through the plasma membrane and bind to internal receptors. • Water-soluble -are unable to pass freely through the plasma membrane due- polarity and must bind to an extracellular domain of a cell-surface receptor. • Other types of ligands can include gases, such as nitric oxide, which can freely diffuse through the plasma membrane and bind to internal receptors. Types of signaling molecules

10. Phosphorylation, the addition of a phosphate group to a molecule such as a protein, is one of the most common chemical modifications that occurs in signaling pathways. • The activation of second messengers, small molecules that propagate a signal, is a common event after the induction of a signaling pathway. • Calcium ion, cyclic AMP, and inositol phospholipids are examples of widely-used second messengers. Methods of Intracellular Signaling

11. Long-distance signaling Blood vessel Endocrine cell Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Figure 11.4 C Examples -Long Distance • 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 • Hormones in animals are often transported in the blood

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

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

14. Earl W. Sutherland’sThree Stages of Cell Signaling - suggested that cells receiving signals went through three processes • Reception • Transduction • Response

15. Step One - Reception • Reception occurs when a signal molecule binds to a receptor protein, causing it to change shape Receptor protein is on the cell surface

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

17. Step Two - Transduction The binding of the signal molecule alters the receptor protein The signal usually starts a cascade of reactions known as a signal transduction pathway Multistep pathways can amplify a signal

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

19. G protein • G proteins ( guanine nucleotide-binding protein) act as molecular switches inside cells, and are involved in transmitting signals from outside a cell to its interior. • Signal results in the release of GDP and the binding of abundant GTP. After a short period of time they hydrolyze GTP and come back to their “off” state. • These proteins change between an active conformation when bound to GTP, and an inactive conformation when bound to GDP. • IN the absence of a signal they are bound to GDP.

20. Protein Kinases • Upon activation they add phosphate groups to themselves and/or other proteins at either serine/threonine, or at tyrosine residues. • Their activity can be regulated by second messengers, interaction with other proteins, or by phosphorylation itself. They are opposed by phosphatases that remove phosphate groups from specific phosphorylated proteins.

21. Gene Expression • Increase in Cellular Metabolism • Cell Growth • Cell Death • Termination of the Signal Cascade Response to the Signal

22. Gene Expression • Gene expression, vital for cells to function properly, is the process of turning on a gene to produce RNA and protein. • This mechanism to control when a gene is expressed; how much of the protein is made; and when it is time to stop making that protein b/c not needed. • conserves energy and space. • Malfunctions of gene expression are detrimental and can lead to many diseases, such as cancer.

23. Increase in Cellular Metabolism • AMP-activated protein kinase (AMPK) plays a key role as a master regulator of cellular energy homeostasis. The kinase is activated in response to stresses that deplete cellular ATP supplies • Cyclic AMP activates PKA (protein kinase A), which phosphorylates two enzymes. • Phophorylation of the first enzyme promotes the degradation of glycogen by activating intermediate GPK that in turn activates GP, which catabolizes glycogen into glucose. • Phosphorylation of the second enzyme, glycogen synthase (GS), inhibits its ability to form glycogen from glucose. • The inhibition of glucose to form glycogen prevents glycogen degradation and synthesis, so glucose is then available for use by the muscle cell.

24. Cell Growth • Normally, cells do not divide unless they are stimulated by signals from other cells. • Most growth factors, which promote cell growth, bind to cell-surface receptors that are linked to tyrosine kinases. • MAP kinase stimulates the expression of proteins that interact with other cellular components to initiate cell division. • Uncontrolled cell growth leads to cancer.

25. Cell Death • Apoptosis- controlled manner of degradation- prevents the release of damaging molecules from inside the cell. • Checkpoints to monitor a cell's health; if abnormalities are detected, a cell can also spontaneously initiate apoptosis. • In some cases, such as a viral infection or cancer, the cell's checks fail. • External signaling can also initiate apoptosis. • For normal embryological development; unnecessary cells that appear during the early stages of development will eventually be eliminated via cell signaling. Formation of toes- mouse paw

26. Termination of the Signal Cascade • The chain of events that conveys the signal through the cell is a signaling pathway/cascade. • Phosphorylation, a component of signal cascades, adds a phosphate group to proteins- changing shape and activating or inactivating the protein. • Degrading or removing the ligand so it can no longer access its receptor terminates the signal. • Enzymes like phosphotases can remove phosphate groups on proteins during dephosphorylation and reverse the cellular modifications produced by signaling cascades.

27. Quorum sensing and biofilms –TED TALKS Biofilm on teeth