BIO201 Cell Communication 2024-2025 PDF

BIO201 - USEK 2024-2025 Chapter 8 1 Cell Communication BIO201 - USEK 2024-2025 2 Cellular Messaging  Cell-to-cell communication is essential for both multicellul...

BIO201 - USEK 2024-2025 Chapter 8 1 Cell Communication BIO201 - USEK 2024-2025 2 Cellular Messaging  Cell-to-cell communication is essential for both multicellular and unicellular organisms  Biologists have discovered some universal mechanisms of cellular regulation  Cells most often communicate with each other via chemical signals  E.g. the fight-or-flight response is triggered by epinephrine (=adrenaline)  The combined effects of multiple signals determine cell response  E.g. the dilation of blood vessels is controlled by multiple molecules 1 BIO201 - USEK 2024-2025 3 CHAPTER 8 OUTLINE I. External signals II. Reception III. Transduction IV. Response V. Apoptosis BIO201 - USEK 2024-2025 4 I- External signals External signals are converted to responses within the cell 2 BIO201 - USEK 2024-2025 5 I.1- Evolution of Cell Signaling  Microbes provide a glimpse of the role of cell signaling in the evolution of life  The yeast, Saccharomyces cerevisiae, has two mating types, a and α  Cells of different mating types locate each other via secreted factors specific to each type BIO201 - USEK 2024-2025 6 3 BIO201 - USEK 2024-2025 7 I.1- Evolution of Cell Signaling  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  Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes  E.g. The concentration of signaling molecules allows bacteria to detect population density (quorum sensing) BIO201 - USEK 2024-2025 8 4 BIO201 - USEK 2024-2025 9 I.2- Local and Long-Distance Signaling  Cells in a multicellular organism communicate by chemical messengers  Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells  In local signaling, animal cells may communicate by direct contact, or cell-cell recognition BIO201 - USEK 2024-2025 10 5 BIO201 - USEK 2024-2025 11 I.2- Local and Long-Distance Signaling  In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances  In long-distance signaling, plants and animals use chemicals called hormones  The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal BIO201 - USEK 2024-2025 12 I.2- Local and Long-Distance Signaling 6 BIO201 - USEK 2024-2025 13 I.3- The Three Stages of Cell Signaling: A Preview  Earl W. Sutherland discovered how the hormone epinephrine (=adrenaline) acts on cells(Nobel prize – 1971)  Sutherland suggested that cells receiving signals went through three processes: 1. Reception  Detection of a signaling molecule by target cell (chemical signal binds to receptor) 2. Transduction  Change of the receptor protein after binding to ligand 1st step of transduction  =conversion of the signal into a form that can trigger a specific response 3. Response  Any cellular activity initiated by the signaling BIO201 - USEK 2024-2025 14 I.3- The Three Stages of Cell Signaling: A Preview 7 BIO201 - USEK 2024-2025 15 I.3- The Three Stages of Cell Signaling: A Preview BIO201 - USEK 2024-2025 16 II- Reception A signaling molecule binds to a receptor protein, causing it to change shape 8 BIO201 - USEK 2024-2025 17  The binding between a signal molecule (ligand) and its receptor is highly specific  A signaling molecule binds to a receptor protein, causing it to change shape  A shape change in a receptor is often the initial transduction of the signal  Most signal receptors are plasma membrane proteins BIO201 - USEK 2024-2025 18 II.1- Receptors in the Plasma Membrane  Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasmamembrane  There are three main types of membrane receptors:  G protein-coupled receptors (GPCRs)  Receptor tyrosine kinases(RTKs)  Ion channel receptors 9 BIO201 - USEK 2024-2025 19 II.1- Receptors in the Plasma Membrane 1. G protein-coupled receptors (GPCRs)  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  If GTP is bound, the G protein is active BIO201 - USEK 2024-2025 20 II.1- Receptors in the Plasma Membrane 1. G protein-coupled receptors (GPCRs) 10  023 BIO201 - USEK 2024-2025 21 II.1- Receptors in the Plasma Membrane BIO201 - USEK 2024-2025 22 II.1- Receptors in the Plasma Membrane 2. Receptor tyrosine kinases (RTKs)  RTKs are membrane receptors that attach phosphates to tyrosines  can trigger multiple signal transduction pathways at once  Abnormal RTKs that function even in the absence of signaling molecules are associated with many kinds of cancer. 11 BIO201 - USEK 2024-2025 23 BIO201 - USEK 2024-2025 24 II.1- Receptors in the Plasma Membrane 3. Ligand-Gated Ion Channel Receptors  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 Ca2+ through a channel in thereceptor 12 BIO201 - USEK 2024-2025 25 BIO201 - USEK 2024-2025 26 II.2- Intracellular Receptors  Intracellular receptor proteins are found in the cytosol or nucleus of target cells  Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors  E.g. steroid and thyroid hormones of animals  An activated hormone-receptor complex can act as a transcription factor, turning on specific genes 13 BIO201 - USEK 2024-2025 27 BIO201 - USEK 2024-2025 28 III- Transduction Cascades of molecular interactions relay signals from receptors to target molecules in the cell 14 BIO201 - USEK 2024-2025 29  Signal transduction usually involves multiple steps  amplify a signal: A few molecules can produce a large cellular response  provide more opportunities for coordination and regulation of the cellular response BIO201 - USEK 2024-2025 30 III.1- Signal Transduction Pathways  Series of steps by which a signal on a cell’s surface is converted into a specific cellular response  Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated  The molecules that relay a signal from receptor to response are mostly proteins  At each step, the signal is transduced into a different form, usually a shape change in a protein  In many pathways, the signal is transmitted by a cascade of protein phosphorylations  Protein kinases transfer phosphates from ATP to protein = phosphorylation  Protein phosphatases remove the phosphates from proteins = dephosphorylation  This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off 15 BIO201 - USEK 2024-2025 31 BIO201 - USEK 2024-2025 32 III.2- Small Molecules and Ions as Second Messengers  Sometimes non-protein molecules are involved in signal transduction: second messengers  The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger”  Second messengers:  Small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion  participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases  Cyclic AMP (cAMP) and calcium ions are common second messengers 16 BIO201 - USEK 2024-2025 33 III.2- Small Molecules and Ions as Second Messengers Cyclic AMP (cAMP)  One of the most widely used second messengers  Produced by adenylyl cyclase  enzyme in the plasma membrane  converts ATP to cAMP in response to an extracellular signal BIO201 - USEK 2024-2025 34 III.2- Small Molecules and Ions as Second Messengers Cyclic AMP (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 (PKA), which phosphorylates various other proteins  Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase 17 BIO201 - USEK 2024-2025 35 BIO201 - USEK 2024-2025 36 III.2- Small Molecules and Ions as Second Messengers Calcium Ions and Inositol Triphosphate (IP3)  Calcium ions (Ca2+) 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 (IP3) and diacylglycerol (DAG) as additional second messengers 18 BIO201 - USEK 2024-2025 37 III.2- Small Molecules and Ions as Second Messengers BIO201 - USEK 2024-2025 38 19 BIO201 - USEK 2024-2025 39 BIO201 - USEK 2024-2025 40 IV- Response Cell signaling leads to regulation of transcription or cytoplasmic activities 20 BIO201 - USEK 2024-2025 41 IV.1- Nuclear and Cytoplasmic Responses  Cell’s response to an extracellular signal sometimes called the “output response”  Signal transduction pathway leads to regulation of one or more cellular activities  Response may occur in the cytoplasm or involve action in the nucleus  Many signaling pathways regulate the synthesis of enzymes or other proteins (by turning genes on or off in the nucleus)  Final activated molecule may function as a transcription factor BIO201 - USEK 2024-2025 42 21 BIO201 - USEK 2024-2025 43 IV.1- Nuclear and Cytoplasmic Responses  Other pathways regulate the activity of enzymes rather than their synthesis  Signaling pathways can also affect the overall behavior of a cell  E.g. changes in cell shape BIO201 - USEK 2024-2025 44 22 BIO201 - USEK 2024-2025 45 IV.2- Fine-Tuning of the Response  Multistep pathways have two important benefits:  Amplifying the signal (and thus the response)  Contributing to the specificity of the response Signal amplification  Enzyme cascades amplify the cell’s response  At each step, the number of activated products is much greater than in the preceding step BIO201 - USEK 2024-2025 46 IV.2- Fine-Tuning of the Response The Specificity of Cell Signaling and Coordination of the Response  Different kinds of cells have different collections of proteins  allow cells to detect and respond to different signals  Even the same signal can have different effects in cells with different proteins and pathways  Pathway branching and “cross-talk” further help the cell coordinate incoming signals 23 BIO201 - USEK 2024-2025 47 IV.2- Fine-Tuning of the Response BIO201 - USEK 2024-2025 48 IV.2- Fine-Tuning of the Response Termination of the Signal  Inactivation mechanisms are an essential aspect of cell signaling  When signal molecules leave the receptor, the receptor reverts to its inactive state 24 BIO201 - USEK 2024-2025 49 V- Apoptosis Apoptosis (programmed cell death) integrates multiple cell-signaling pathways BIO201 - USEK 2024-2025 50 V.1- Definition  Apoptosis is programmed or controlled cell suicide  Cell is chopped and packaged into vesicles that are digested by scavenger cells  prevents enzymes from leaking out of a dying cell and damaging neighboring cells 25 BIO201 - USEK 2024-2025 51 V.2- Role in embryonic development  Apoptosis is important in shaping an organism during embryonic development  Role first studied in Caenorhabditis elegans  apoptosis results when specific proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis BIO201 - USEK 2024-2025 52 V.2- Role in embryonic development 26 BIO201 - USEK 2024-2025 53 V.2- Role in embryonic development BIO201 - USEK 2024-2025 54 V.3- Apoptotic Pathways and the Signals That Trigger Them  Caspases are the main proteases 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 allanimals  Apoptosis may be involved in some diseases  E.g. Parkinson’s and Alzheimer’s  Interference with apoptosis may contribute to some cancers 27 BIO201 - USEK 2024-2025 55 You Should Now Be Able To: 1. Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system 2. Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand-gated ion channels 3. List two advantages of a multistep pathway in the transduction stage of cell signaling 4. Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell 5. Define the term second messenger; briefly describe the role of these molecules in signaling pathways 6. Explain why different types of cells may respond differently to the same signal molecule 7. Describe the role of apoptosis in normal development and degenerative disease in vertebrates 28