1306SU22_Cell Communication.pdf

Cell Connections and Communication BIOL 1306: Biology 1 for Majors Jenifer Gifford, Ph.D. [email protected] 1. Describe the structure and function of the three major cellcell connections. 2. Describe the structure and function of the ECM 3. Compare and contrast the four types of signaling 4. Explain...

Cell Connections and Communication BIOL 1306: Biology 1 for Majors Jenifer Gifford, Ph.D. [email protected] 1. Describe the structure and function of the three major cellcell connections. 2. Describe the structure and function of the ECM 3. Compare and contrast the four types of signaling 4. Explain the roles of ligands, receptors, signaling proteins, and effector proteins in transmitting information from the outside of the cell to the inside 5. Describe how signaling mechanisms are regulated 6. Compare and contrast the three major types of receptors 7. State the role of second messengers 1 In multicellular organisms, cells are connected to other cells • Direct physical connections between cells is the basis of multicellularity. These connections maintain structure and function of tissues • Cell–cell attachments in multicellular organisms are composed of proteins and fibers that bind cells together. This is especially important in epithelia—tissues that line surfaces • Structures that hold cells together vary among different organisms 2 Three Major Connections Link Animal Cells Together Side By Side Tight Junctions: • Composed of proteins from each cell that bind together. • Form waterproof seals Three Major Connections Link Animal Cells Together Side By Side • • Gap junctions were discussed during membrane transport because they formed channels between cells and are involved in transporting molecules back and forth. Gap junctions can transport molecules that may: • regulate gene expression, altering which proteins are produced and which are not • activate or inactivate particular proteins that already exist in the cell— often those involved in metabolism, membrane transport, secretion, and the cytoskeleton. 3 Three Major Connections Link Animal Cells Together Side By Side Desmosomes are made of cadherins and link the cytoskeleton of cells together so that they can sense changes in adjacent cells. Three Major Connections Link Animal Cells Together Side By Side • Cadherins are useful for sorting cells into structures during development. • There are several variations of cadherin proteins and identical cadherins like to associate with each other • If you dissociate amphibian embryos into single cells and then allow them to attempt to reassemble into the proper layers, it can do so very closely to the original embryonic structure. 4 The plasma membrane of cells is also connected to extracellular structures Layers beyond the plasma membrane are made of materials secreted by the cells and function to provide support to the cells and resist damaging tension. Extracellular Layers Vary Across the Domains of Life Bacterial cell walls consist primarily of the peptidoglycan Archaeal cell walls have an absence of peptidoglycan and instead have other proteins that form dense coat of proteins (S-layer) Plants cells are surrounded by a cell wall made of cellulose. Cellulose is bundled into cable-like microfibrils connected by pectin. 5 Extracellular Layers Across the Domains of Life • New plant cells secrete fibrous material in the form of cellulose to form the primary cell wall which defines the shape of plant cell and counteracts the turgor pressure the cell experiences as water enters cell via osmosis • Mature plant cells secrete secondary cell wall between plasma membrane and primary cell wall. The structure varies depending on the part of the plant. • In leaf cells, it contains waxes • In cells that form wood, it contains lignin The Extracellular Matrix of Animal Cells • • Animal cells possess an Extracellular Matrix (ECM), which is a protective layer beyond the plasma membrane. The ECM of the eukaryotic animal cell: • Is composed of mainly fibrous collagen and elastin as well as a ground substance of proteoglycans that are secreted by the cell. • Helps define cell shape • Resists compression • Acts as a first defense • Can attach the plasma membrane to other cells 6 Cell Membranes Are Connected to the ECM Integrins are membrane proteins that anchor the cytoskeleton of a cell to the ECM. They bind to laminins in the ECM, which are major linking molecules throughout the substance. When multiple cells link to the same laminin molecules they are indirectly connected Attachment to the ECM is a matter of life and death • When connected to the ECM cells receive signals that they are in the right environment and should thrive. • When these linkages (integrin to the ECM) break down, the cell begins a signaling process to initiate its own death. • This leads to the next topic. How to cells change their behavior in response to their environment and other cells? 7 Example of Cellular Signaling and Behavior: Angiogenesis Capillary like vessels grow off of main vessels towards tumors to provide sugar and oxygen Blood Vessels Angiogenesis Tumors require nutrients, just like healthy cells Tumor Cells Growth Factors (VEGF) Endothelial Cells Tumor cells secrete growth factors (small proteins) that bind to receptors on the endothelial cells. This causes the endothelial cells to divide and grow toward the tumor 8 Distant Cells Communicate Via Signal Transduction Contact Dependent Signaling is important during development and immune responses. Requires that cells being in direct membrane to membrane contact through mechanism such as a membrane bound signaling molecule recognized by a receptor on a target cell. Distant Cells Communicate Via Signal Transduction Paracrine Signaling depends on the local mediators that are released into the extracellular space and act on neighboring cells. The signaling and target cells can be different cell types 9 Distant Cells Communicate Via Signal Transduction Synaptic Signaling is performed by neurons that transmit signals electrically along their axons and release neurotransmitters at synapses, which are often located relatively far away from the cell body. Chemical signals are in the form of neurotransmitters released from the long branching axon at a synapse. Distant Cells Communicate Via Signal Transduction Endocrine Signaling depends on endocrine cells which secrete hormones into the bloodstream for distribution throughout the body. This type of signaling allows the longest distance of travel for signaling molecules. 10 Principles of Signal Transduction Communication between cells in multicellular organisms is mediated mainly by extracellular signaling molecules (ligands). Most cells can emit and receive signals. Upstream Receptor proteins receive and transmit the signal from the ligand across the membrane. A cascade/pathway involves the transmittance of this signal through multiple signaling proteins. Downstream Effector proteins at the end of the pathway are altered by the incoming signal and effect change. Lets Think about the Signaling Molecules: Recall the Components and Properties of the Plasma Membrane The membrane is made of amphipathic phospholipids with a nonpolar/fatty core. What kinds of molecules can travel across the membrane without help? 11 Characteristics of Different Signaling Molecules • Lipid-insoluble do not cross plasma membrane: • Have to be recognized at cell surface • Receptors are on cell’s plasma membrane • Lipid-soluble signaling molecules diffuse across plasma membrane: • Receptors are in target cells’ cytoplasm Characteristics and Behavior of Different Signaling Molecules: Lipid Soluble • Steroid Hormones are examples of a lipid soluble signaling molecule. • Estrogen • Cortisol • Released by a carrier protein. • Receptors are inside the cell rather than on the membrane. • Hormone Receptor complex affects gene expression. • This affects protein expression 12 Characteristics and Behavior of Different Signaling Molecules: Lipid Insoluble Soluble • Lipid insoluble (polar) molecules cannot diffuse through the membrane. • Recognized at the cell surface by a specific receptor. • Triggers signal transduction which ultimately affects gene expression and protein production. • This leads to responses in cell behavior. Signaling Molecules Bind to Receptors; Multiple Types of Receptors Exist We’re going to focus on these two 13 We’re Focusing on Two Types of Receptors Two types of signal transduction receptors: 1. G-protein-coupled receptors (GPCR): • Initiate production of intracellular second messengers 2. Enzyme-linked receptors • phosphorylate proteins inside target cell G-Proteins are Regulated by GTP/GDP • • G proteins—peripheral membrane proteins G coupled protein receptors (GPCR) respond to a signaling molecule and activate G Proteins. • G Proteins are fully activated by binding to GTP 14 G-Proteins are Regulated by GTP/GDP • When G proteins are activated by GPCR’s+GTP they trigger the production of second messengers, which are small, nonprotein signaling molecules or ions Second Messengers Second messengers: • Are effective because they are small molecules • Can be produced quickly in large quantities • Diffuse rapidly throughout cell which amplifies signals • Are not restricted to a single role • The same second messenger can have different roles in different cells while receiving the same signal • More than one type may be involved in triggering cell response Name Calcium ion Type of Response (Ca2+) Binds to a protein called calmodulin; C a2+/calmodulin complex then activates proteins Cyclic adenosine monophosphate (cA MP) Activates certain protein kinases Cyclic guanosine monophosphate (cG MP) Opens ion channels; activates certain protein kinases Diacylglycerol (DAG) Activates certain protein kinases Inositol trisphosphate (IP3) Opens calcium channels, allowing stored calcium ions to enter cytosol 15 Second Messengers Can Activate Downstream Kinases Some second messengers are used to activate protein kinases later in the pathway: • Kinases add phosphate group to other proteins • Activate or deactivate other proteins Phosphatases are proteins that remove phosphate groups Enzyme Linked Receptors • Enzyme-linked receptors: • Transmembrane proteins • Directly catalyze reaction inside cell • Often phosphorylate themselves or target molecules once activated • Receptor tyrosine kinases (RTKs) are the best-known group of enzyme-linked receptors 16 Enzyme Linked Receptors Mitogens often stimulate RTKs and cause cell division Principles of Signal Transduction • Signal receptors are dynamic: • Number of receptors in cell may change • Ability of receptor to bind signaling molecules may change • Sensitivity of cell to particular signaling molecule may change over time 17 Principles of Signal Transduction • Signal receptors can be blocked: • Ex. Beta-blockers are drugs that reduce your blood pressure by slowing your heart rate • These drugs are used to block interaction between molecules such as epinephrine (ligand) and their receptors Connections to Cancer Treatments Breast Cancers are characterized by the types of receptors they have in their plasma membranes: • Estrogen Receptors (ER) • HER2 Receptors • Progesterone Receptors (PR) • Triple Negative Breast Cancer What kind of signaling molecule is estrogen? 18 Connections to Cancer Treatments Signal receptors can be blocked: Last Note: Signal Transduction is a web of interconnecting pathways that affect cell behavior Crosstalk integrates diverse signals that cell receives from multiple pathways: • One pathway may inhibit steps in second pathway thus reducing the cell’s response to second pathway • One pathway may stimulate steps in second pathway leading to two different responses to the signal • Multiple steps in signaling pathway provide many points for crosstalk to occur 19 Signal Transduction is a web of interconnecting pathways that affect cell behavior Connecting Angiogenesis to its Pathway • The bottom of every pathway can have unique outcomes. • Many pathways change gene expression • Gene expression leads to protein production. • New proteins = New functions= New Behavior 20 Main Points 1. Cells use a variety of proteins to form connections with one another to behave cooperatively form tissues (tight junctions, gap junctions, desmosomes, as well as connections to the ECM) 2. Cells not attached to one another communicate via signal transduction. 1. This allows the cell to respond to signals and adjust it’s behavior accordingly. 2. Four major types of signaling (contact, paracrine, synaptic, endocrine) 3. Two major types of signaling molecules (lipid soluble and insoluble) and receptors (GPCR and Enzyme Coupled Receptors) 4. Pathways are not isolated and some can inhibit or stimulate one another (Crosstalk) 21