Cell Connections and Communication PDF

Cell Connections and Communication BIOL 1306: Biology 1 for Majors Jenifer Gifford, Ph.D. [email protected] In Unit 1 We Learned Biomolecules build membranes and organelles, which coordinate...

Cell Connections and Communication BIOL 1306: Biology 1 for Majors Jenifer Gifford, Ph.D. [email protected] In Unit 1 We Learned Biomolecules build membranes and organelles, which coordinate functions to power cells Functioning cells grow and divide through mitosis to create multicellular organisms 1  In this Lecture, We Will Learn: Mitosis and other cellular phenomena are the result of cellular signaling As cells grow and divide (proliferate) they form connections to one another to form functional tissues. Overall Importance: The ability for cells to exist in social contexts is the foundation for building whole organisms 1. Compare and contrast the types of signaling 2. Explain the roles of ligands, receptors, signaling proteins, and effector proteins in transmitting information from the outside of the cell to the inside 3. Describe how signaling mechanisms are regulated 4. Compare and contrast the three major types of receptors 5. State the role of second messengers 6. Describe the structure and function of the three major cell- cell connections. 7. Describe the structure and function of the ECM 2  Example of Cellular Signaling and Behavior: Wound Healing and Mitosis Cell division is a response to growth factor signals. Specific signals activate gene expression for proteins that move the cell cycle forward, like cyclins 3  Example of Cellular Signaling and Behavior: Angiogenesis Capillary like vessels grow off of main vessels towards tumors to provide sugar and oxygen Tumor cells secrete growth Blood Vessels factors (small proteins) that Angiogenesis bind to receptors on the endothelial Tumors require cells. This causes nutrients, just like the endothelial healthy cells Tumor Cells Growth Factors (VEGF) cells to divide Endothelial Cells and grow toward the tumor Short Distance Cell Signaling Contact Dependent Signaling is Paracrine Signaling depends on important during development and the local mediators that are immune responses. released into the extracellular space and act on neighboring Requires that cells being in direct membrane to membrane contact cells. through mechanism such as a The signaling and target cells membrane bound signaling molecule can be different cell types recognized by a receptor on a target Autocrine Signaling is signaling cell. to oneself 4  Long Distance Cell Signaling Synaptic Signaling is performed by Endocrine Signaling depends on neurons that transmit signals electrically endocrine cells which secrete hormones along their axons and release into the bloodstream for distribution neurotransmitters at synapses, which throughout the body. are often located relatively far away from the cell body. This type of signaling allows the longest distance of travel for signaling molecules. Principles of Signal Communication between cells in Transduction 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. Effector proteins at the end of the pathway are altered by the Downstream incoming signal and effect change. 5  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? 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 6  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 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. 7  Signaling Molecules Bind to Receptors; Multiple Types of Receptors Exist We’re going to focus on these two right now We’re Focusing on Two Types of SURFACE 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 8 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 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 9  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 NO NEED TO MEMORIZE Name Type of Response Calcium ion (Ca2+) Binds to a protein called calmodulin; C a2+/calmodulin complex then activates proteins Cyclic adenosine Activates certain protein kinases monophosphate (c AMP) Cyclic guanosine Opens ion channels; activates certain monophosphate (c protein kinases GMP) Diacylglycerol (DA Activates certain protein kinases G) Inositol Opens calcium channels, allowing trisphosphate (IP3) stored calcium ions to enter cytosol 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 Recall: CDK’s phosphorylated targets to activate mitotic events Activate or deactivate other proteins Phosphatases are proteins that remove phosphate groups 10  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 a type of enzyme-linked receptors Enzyme Linked Receptors Mitogens/Growth factors often stimulate RTKs and cause cell division 11  Principles of Signal Transduction Signal receptors can be blocked/inhibited: 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 What kind of signaling molecule is the types of receptors they have in estrogen? their plasma membranes: Estrogen Receptors (ER) HER2 Receptors Progesterone Receptors (PR) Triple Negative Breast Cancer 12  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 13  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 14 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 15  Three Major Connections Link Animal Cells Together Side By Side (1) Tight Junctions: Composed of proteins from each cell that bind together. Form waterproof seals Three Major Connections Link Animal Cells Together Side By Side (2) 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. 16  Three Major Connections Link Animal Cells Together Side By Side (3) 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 also 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. 17  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) Plant cells are surrounded by a cell wall made of cellulose. Cellulose is bundled into cable-like microfibrils connected by pectin. 18  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 19  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? 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