Topic 2: Chpt 6-7 Flashcards
What are the four basic methods of cell-to-cell communication in the body?
-Local communication via gap junctions, allowing direct cytoplasmic transfer of signals between adjacent cells.
-Contact-dependent signals, occurring when surface molecules on one cell bind to surface molecules on another cell.
-Communication through chemicals that diffuse through the extracellular fluid to act on nearby cells.
-Long-distance communication, utilizing chemical and electrical signals carried by nerve cells and chemical signals transported in the blood.
How are gap junctions formed, and what molecules can pass through them?
Gap junctions are formed from the union of membrane-spanning proteins called connexins on two adjacent cells. These connexins create protein channels called connexons, through which ions and small molecules such as amino acids, ATP, and cyclic AMP (cAMP) can diffuse directly from the cytoplasm of one cell to the cytoplasm of the next.
What is the function of connexins in gap junctions?
Connexins are membrane-spanning proteins that form the protein channels (connexons) of gap junctions. They allow for the direct transfer of electrical and chemical signals between adjacent cells, enabling coordinated responses among cell populations.
How can the movement of molecules and electrical signals through gap junctions be regulated?
the movement of molecules and electrical signals through gap junctions can be modulated or shut off completely. While ions and small molecules can freely diffuse through open gap junctions, larger molecules are unable to pass. Additionally, the opening and closing of gap junctions can be regulated, influencing the extent of communication between neighboring cells.
Where are gap junctions found in the body, and what is their significance?
Gap junctions are found in almost every cell type in mammals, including heart muscle, some types of smooth muscle, lung, liver, and neurons of the brain. Their widespread presence underscores their importance in facilitating direct cell-to-cell communication, essential for coordinated physiological processes and responses.
What is contact-dependent signaling, and where does it occur?
Contact-dependent signaling involves the binding of surface molecules on one cell membrane to a membrane protein of another cell. It occurs in various biological processes, including immune responses and during growth and development, such as in the extension of nerve cell projections
What are cell adhesion molecules (CAMs), and how do they participate in cell-to-cell signaling?
Cell adhesion molecules (CAMs) are proteins initially recognized for their role in cell-to-cell adhesion. They have been found to act as receptors in cell-to-cell signaling, facilitating communication between neighboring cells. CAMs are linked to the cytoskeleton or intracellular enzymes, allowing for bidirectional signal transmission across cell membranes.
What is another term for contact-dependent signaling?
Contact-dependent signaling is also known as juxtacrine signaling. It describes the process by which signals are transmitted directly between neighboring cells through physical contact between their membrane-bound molecules
How do cell adhesion molecules transfer signals across cell membranes?
Cell adhesion molecules (CAMs) transfer signals across cell membranes through linkages to the cytoskeleton or intracellular enzymes. These linkages allow for the bidirectional transmission of signals, enabling coordinated responses between adjacent cells.
Can you provide an example of contact-dependent signaling in biological processes?
An example of contact-dependent signaling is observed during growth and development when nerve cells extend long projections that must grow from the central axis of the body to the distant ends of developing limbs. In this process, interactions between membrane-bound molecules on neighboring cells guide the directional growth of nerve cell extensions.
What is paracrine signaling?
Paracrine signaling involves the release of chemical signals by a cell, which act on nearby cells in the immediate vicinity of the secreting cell. These signals, called paracrine signals, diffuse through the interstitial fluid to reach their target cells
Define autocrine signaling.
Autocrine signaling occurs when a cell releases chemical signals that act on the same cell that secreted them. The signals, known as autocrine signals, bind to receptors on the secreting cell, affecting its own behavior or function.
What is the function of hormones in the endocrine system?
Hormones are chemical signals secreted into the bloodstream by endocrine glands. They travel throughout the body and interact with target cells that possess specific receptors for the hormone. Hormones regulate various physiological processes and coordinate the activities of different organs and tissues.
How do cells become target cells for hormones?
Target cells for hormones are those cells that possess specific receptors for the hormone. These receptors are typically proteins located on the cell membrane or inside the cell. Only cells with receptors for a particular hormone can respond to its signaling effects.
What is the difference between a neurotransmitter and a neuromodulator?
A neurotransmitter is a neurocrine molecule that diffuses across a narrow extracellular space from a neuron to a target cell and has a rapid-onset effect. In contrast, a neuromodulator acts more slowly as an autocrine or paracrine signal, influencing the activity of nearby neurons or modulating neurotransmitter release
What is a neurohormone, and how does it differ from other neurocrine molecules?
A neurohormone is a neurocrine molecule that diffuses into the bloodstream for body-wide distribution. Unlike neurotransmitters, which act locally, neurohormones have systemic effects and can influence distant target cells throughout the body.
What are cytokines, and how have they been broadly classified?
Cytokines are regulatory peptides that modulate immune responses and control cell development and differentiation. They are characterized by their structure of four or more α-helix bundles. Cytokines have been classified into families, including interferons, interleukins, colony-stimulating factors, growth factors, tumor necrosis factors, and chemokines.
What is the primary association of cytokines in the body?
Cytokines are primarily associated with immune responses, such as inflammation. However, they also play crucial roles in cell development and differentiation processes.
How do cytokines differ from classic hormones?
Cytokines differ from classic hormones in several ways. Firstly, cytokines are not produced exclusively by specialized epithelial cells; instead, any nucleated cell can secrete cytokines at some point in its life span. Secondly, cytokines are made on demand, unlike protein or peptide hormones that are pre-made and stored in endocrine cells until needed. Finally, the intracellular signal pathways for cytokines typically differ from those for hormones.
What are the common features shared by all signal pathways?
-The signal molecule, also known as a ligand, binds to a protein receptor. The ligand serves as the first messenger, bringing information to the target cell.
-Ligand-receptor binding activates the receptor.
-The activated receptor subsequently activates one or more intracellular signal molecules.
-The final signal molecule in the pathway generates a response by modifying existing proteins or initiating the synthesis of new proteins.
How do lipophilic and lipophobic signal molecules differ in their interaction with cells?
Lipophilic signal molecules enter cells by simple diffusion through the phospholipid bilayer of the cell membrane, where they bind to cytosolic or nuclear receptors. On the other hand, lipophobic signal molecules remain in the extracellular fluid and bind to receptor proteins on the cell membrane.
What are the major categories of membrane receptors, and how do they function?
The major categories of membrane receptors include chemically gated ion channels (receptor-channels), G protein-coupled receptors, receptor-enzymes, and integrin receptors. These receptors transmit information from signal molecules across the membrane to initiate an intracellular response, a process known as signal transduction.
What is signal transduction, and how does it occur?
Signal transduction is the process by which an extracellular signal molecule activates a membrane receptor, leading to alterations in intracellular molecules and ultimately resulting in a cellular response. Extracellular signal molecules are known as first messengers, while the intracellular molecules form a second messenger system
What is the role of transducers in signal transduction?
Transducers in biological systems, typically membrane proteins, convert the message of extracellular signals into intracellular messenger molecules. These transducers essentially “translate” the extracellular signal into a form that can initiate cellular responses.
The basic pattern of a signal transduction pathway involves the following events:
- An extracellular signal molecule, known as the first messenger, binds to and activates a membrane receptor.
- The activated membrane receptor initiates an intracellular cascade of second messengers by activating associated proteins.
- The last second messenger in the cascade acts on intracellular targets to generate a cellular response.
The intracellular events in basic signal transduction pathways include:
- Membrane receptors and associated proteins activate either:
(a.) Protein kinases, enzymes that transfer a phosphate group from ATP to a protein, thereby regulating cellular processes through phosphorylation.
(b.) Amplifier enzymes that generate intracellular second messengers.
- Second messenger molecules can:
(a.) Alter the gating of ion channels, affecting the cell’s membrane potential.
(b.) Increase intracellular calcium levels, leading to changes in protein function.
(c.) Change enzyme activity, particularly of protein kinases or protein phosphatases, which can modify protein configuration through phosphorylation or dephosphorylation.
- Proteins modified by calcium binding and phosphorylation are responsible for the cellular response to the signal, which can include alterations in enzyme activity and the opening or closing of gated ion channels.
How does a signaling cascade typically start, and what does it involve?
A signaling cascade begins when a stimulus, often a signal molecule, converts an inactive molecule (A, typically the receptor) into its active form. Active A then converts an inactive molecule (B) into its active form. This process continues as active B converts inactive molecule C into active C, and so forth, until the final step where a substrate is converted into a product. Signaling cascades are common in many intracellular signaling pathways, where a series of molecular events amplify and propagate the initial signal.
What is signal amplification in signal transduction pathways, and why is it important?
Signal amplification in signal transduction pathways refers to the process where one signal molecule, typically the first messenger ligand, activates an amplifier enzyme, which in turn activates multiple molecules downstream. This amplification results in the production of multiple second messenger molecules, creating a larger effect compared to a 1:1 ratio between each step. Signal amplification is crucial as it enables a small amount of ligand to produce a significant physiological response, maximizing the efficiency of cellular signaling.
What are ligand-gated ion channels, and how do they initiate intracellular responses?
Ligand-gated ion channels are receptors typically found in nerve and muscle cells. When an extracellular ligand binds to these receptor-channel proteins, a channel gate opens or closes, altering the cell’s permeability to an ion. This change in ion permeability rapidly modifies the cell’s membrane potential, generating an electrical signal that affects voltage-sensitive proteins. This rapid response mechanism triggers various cellular processes, such as muscle contraction in skeletal muscle cells. Examples include acetylcholine-gated ion channels, which allow Na+ and K+ ions to flow through, leading to depolarization and muscle contraction.
What are G protein-coupled receptors (GPCRs), and how do they function?
G protein-coupled receptors (GPCRs) are membrane-spanning proteins that cross the phospholipid bilayer seven times. The cytoplasmic tail of the receptor protein is linked to a three-part membrane transducer molecule known as a G protein. GPCRs bind various ligands, including hormones, growth factors, olfactory molecules, visual pigments, and neurotransmitters. Upon ligand binding, GPCRs activate G proteins, leading to downstream signaling events.
How are G proteins activated?
G proteins are activated when they exchange guanosine diphosphate (GDP) for guanosine triphosphate (GTP). This activation occurs upon ligand binding to the associated GPCR. Inactive G proteins are bound to GDP, while activation results in the exchange of GDP for GTP, leading to conformational changes that enable G protein signaling.
What are the two main actions of activated G proteins?
Upon activation, G proteins either (1) open an ion channel in the membrane or (2) alter enzyme activity on the cytoplasmic side of the membrane. These actions facilitate signal transduction and downstream cellular responses to extracellular stimuli.
What is the significance of G proteins in signal transduction?
G proteins play a crucial role in signal transduction by mediating the response of cells to extracellular stimuli. They serve as intermediaries between activated GPCRs and downstream effector proteins, such as ion channels or enzymes. The activation of G proteins initiates signaling cascades that regulate various cellular processes.
What are the two most common amplifier enzymes associated with G protein-coupled receptors?
Adenylyl cyclase and phospholipase C. These enzymes are activated by G proteins upon ligand binding to GPCRs and catalyze the production of second messengers, such as cyclic AMP (cAMP) and inositol trisphosphate (IP3), which mediate intracellular signaling pathways.
What is the role of adenylyl cyclase in the G protein-coupled adenylyl cyclase-cAMP system?
Adenylyl cyclase is the amplifier enzyme in the G protein-coupled adenylyl cyclase-cAMP system. It converts adenosine triphosphate (ATP) to cyclic AMP (cAMP), which serves as a second messenger molecule in intracellular signaling pathways
What is cyclic AMP (cAMP), and what role does it play in cellular signaling?
Cyclic AMP (cAMP) is a second messenger molecule generated by adenylyl cyclase in the G protein-coupled adenylyl cyclase-cAMP system. It activates protein kinase A (PKA), which phosphorylates other intracellular proteins as part of the signal cascade, leading to cellular responses to extracellular stimuli.
What is the significance of the G protein-coupled adenylyl cyclase-cAMP system in cellular signaling?
The G protein-coupled adenylyl cyclase-cAMP system is a fundamental signaling pathway activated by protein hormones. It regulates various cellular processes by mediating the production of cyclic AMP (cAMP) and subsequent activation of protein kinase A (PKA), leading to phosphorylation of intracellular proteins and cellular responses to extracellular stimuli.
What is the role of phospholipase C (PLC) in some G protein-coupled receptor signaling pathways?
Phospholipase C (PLC) is an amplifier enzyme linked to some G protein-coupled receptors. When activated by a signal molecule, PLC converts a membrane phospholipid, phosphatidylinositol bisphosphate, into two lipid-derived second messenger molecules: diacylglycerol (DAG) and inositol trisphosphate (IP3).
What are the lipid-derived second messenger molecules generated by phospholipase C (PLC) activity?
Phospholipase C (PLC) activity produces two lipid-derived second messenger molecules: diacylglycerol (DAG) and inositol trisphosphate (IP3). DAG remains in the lipid portion of the membrane and interacts with protein kinase C (PKC), while IP3 enters the cytoplasm and binds to a calcium channel on the endoplasmic reticulum (ER).
How does diacylglycerol (DAG) function as a second messenger in cellular signaling?
Diacylglycerol (DAG) is a nonpolar diglyceride produced by phospholipase C (PLC) activity. It remains in the lipid portion of the membrane and interacts with protein kinase C (PKC), which is activated by calcium ions (Ca2+). PKC phosphorylates cytosolic proteins, propagating the signal cascade.
What is the role of inositol trisphosphate (IP3) in cellular signaling?
Inositol trisphosphate (IP3) is a water-soluble messenger molecule generated by phospholipase C (PLC) activity. IP3 binds to a calcium channel on the endoplasmic reticulum (ER), causing it to open and allowing calcium ions (Ca2+) to diffuse out of the ER into the cytosol, where they participate in various cellular processes.
How do diacylglycerol (DAG) and inositol trisphosphate (IP3) contribute to intracellular signaling pathways?
Diacylglycerol (DAG) and inositol trisphosphate (IP3) are second messenger molecules generated by phospholipase C (PLC) activity. They activate downstream signaling pathways, with DAG activating protein kinase C (PKC) and IP3 mobilizing intracellular calcium ions (Ca2+), collectively regulating numerous cellular processes.
What are catalytic receptors, and how do they function?
Catalytic receptors are a type of receptor-enzyme that possess both a receptor region on the extracellular side of the cell membrane and an enzyme region on the cytoplasmic side. Ligand binding to the receptor activates the intracellular enzyme, initiating signaling cascades within the cell
What are the two main types of catalytic receptor enzymes mentioned in the text?
The two main types of catalytic receptor enzymes mentioned are protein kinases, such as tyrosine kinase, and guanylyl cyclase. Tyrosine kinase phosphorylates tyrosine residues on target proteins, while guanylyl cyclase converts GTP to cyclic GMP (cGMP), serving as an amplifier enzyme.
How does the insulin receptor exemplify a catalytic receptor?
The insulin receptor is an example of a catalytic receptor where both the extracellular binding region and the intracellular enzyme region are parts of the same protein molecule. The insulin receptor possesses intrinsic tyrosine kinase activity, which is activated upon ligand binding.
What are cytokine receptors, and how are they associated with intracellular enzymes?
Cytokine receptors are a type of catalytic receptor associated with cytosolic enzymes. Most cytokine receptors are associated with Janus family tyrosine kinases (JAK kinases). Upon ligand binding, cytokine receptors activate JAK kinases, initiating intracellular signaling pathways.
What are the two categories of catalytic receptors based on the organization of their extracellular binding region and intracellular enzyme region?
In one type, such as the insulin receptor, both regions are part of the same protein molecule. In the other type, exemplified by cytokine receptors, the enzyme region is a separate protein activated by ligand binding.
What are integrins, and what roles do they play in cell function?
Integrins are membrane-spanning proteins involved in various cellular processes, including blood clotting, wound repair, cell adhesion and recognition in the immune response, and cell movement during development. These receptors are classified as catalytic receptors and bind to extracellular matrix proteins or ligands such as antibodies and molecules involved in blood clotting. Inside the cell, integrins attach to the cytoskeleton via anchor proteins, enabling them to transmit signals and regulate cytoskeletal organization upon ligand binding.
How do integrin receptors contribute to blood clotting, and what happens when these receptors are absent?
Integrin receptors play a crucial role in blood clotting by mediating platelet function, which is essential for clot formation. In individuals with inherited conditions where integrin receptors are absent, platelets—cell fragments involved in blood clotting—lack these receptors, leading to defective blood clotting. This deficiency highlights the importance of integrin receptors in ensuring proper hemostasis and clot formation.
Describe the structure of integrin receptors and their mechanism of action upon ligand binding.
Integrin receptors span the cell membrane and bind to extracellular matrix proteins or ligands, while inside the cell, they attach to the cytoskeleton via anchor proteins. Upon ligand binding, integrins can activate intracellular enzymes or modulate the organization of the cytoskeleton, thereby initiating signaling cascades that regulate cellular responses and functions.
How are cell responses controlled in basic signal transduction, and what are the categories of modified proteins involved?
Cell responses in basic signal transduction are controlled by modified proteins that can be broadly categorized into four groups: metabolic enzymes, motor proteins for muscle contraction and cytoskeletal movement, proteins regulating gene activity and protein synthesis, and membrane transport and receptor proteins. These modified proteins play essential roles in mediating the cellular responses to extracellular stimuli, thereby regulating various physiological processes within the cell.
What are the different ways calcium ions enter a cell?
Calcium ions can enter the cell through voltage-gated, ligand-gated, or mechanically gated calcium channels. Additionally, calcium can be released from intracellular compartments by second messengers such as IP3. Most intracellular calcium is stored in the endoplasmic reticulum, where it is concentrated by active transport.
What happens when calcium is released into the cytosol?
Release of calcium into the cytosol creates a calcium signal or “spark,” which can be recorded using special calcium imaging techniques. The calcium ions combine with cytoplasmic calcium-binding proteins to exert various effects.
How does calcium exert its effects in the cell?
Calcium binds to cytoplasmic calcium-binding proteins to exert various effects. It can bind to calmodulin, regulatory proteins, ion channels, and other targets to alter enzyme activity, trigger muscle contraction, initiate exocytosis, and regulate ion channel gating.
Provide examples of calcium-dependent events in the cell.
Calcium-dependent events in the cell include muscle contraction initiated by calcium binding to troponin, exocytosis of secretory vesicles such as insulin release from pancreatic beta cells, and alteration of ion channel gating states, among others. Calcium entry into a fertilized egg initiates development of the embryo.
What are some examples of soluble gases that act as paracrine/autocrine signal molecules?
nitric oxide (NO), carbon monoxide, and hydrogen sulfide.
What was the initially named short-lived signal molecule produced by endothelial cells lining blood vessels?
Endothelial-derived relaxing factor (EDRF), which was later identified as nitric oxide (NO).
How is nitric oxide (NO) synthesized in tissues?
Nitric oxide (NO) is synthesized in tissues by the action of the enzyme nitric oxide synthase (NOS) on the amino acid arginine.
What is the role of nitric oxide (NO) in target cells?
Nitric oxide (NO) diffuses into target cells, where it binds to intracellular proteins. In many cases, it binds to the cytosolic form of guanylyl cyclase and causes the formation of the second messenger cGMP. Nitric oxide (NO) also acts as a neurotransmitter and neuromodulator in the brain, in addition to relaxing blood vessels.
What are some effects of carbon monoxide (CO) as a signal molecule?
Carbon monoxide (CO) activates guanylyl cyclase and cGMP, similar to nitric oxide (NO), but it may also work independently to exert its effects. Carbon monoxide targets smooth muscle and neural tissue.
What is the role of hydrogen sulfide (H2S) as a gaseous signal molecule?
Hydrogen sulfide (H2S) also acts in the cardiovascular system to relax blood vessels.
What are orphan receptors?
Orphan receptors are receptors that have no known ligand. Scientists are attempting to identify the ligands that bind to these orphan receptors by working backward through signal pathways.
What are eicosanoids, and how are they derived?
Eicosanoids are lipid-derived paracrine signals that play important roles in many physiological processes. They are derived from arachidonic acid, a 20-carbon fatty acid, and act on their target cells using G protein-coupled receptors.
Describe the synthesis process of eicosanoids.
The synthesis process for eicosanoids involves the arachidonic acid cascade. Arachidonic acid is produced from membrane phospholipids by the enzyme phospholipase A2 (PLA2). Arachidonic acid may act directly as a second messenger or be converted into eicosanoid paracrine signals.
What are the two major groups of arachidonic acid-derived paracrine molecules?
The two major groups are leukotrienes and prostanoids. Leukotrienes are produced by the enzyme lipoxygenase and play a significant role in asthma and anaphylaxis. Prostanoids, produced by the enzyme cyclooxygenase (COX), include prostaglandins and thromboxanes, which act on various tissues in the body.
How do nonsteroidal anti-inflammatory drugs (NSAIDs) work, and what are their potential side effects?
NSAIDs, such as aspirin and ibuprofen, prevent inflammation by inhibiting COX enzymes and decreasing prostaglandin synthesis. However, they are not specific and may cause serious side effects, such as bleeding in the stomach.
What is the significance of the discovery of COX1 and COX2 isozymes?
The discovery of COX1 and COX2 isozymes enabled the design of drugs that target a specific COX isozyme. By inhibiting only COX2, which produces inflammatory prostaglandins, physicians hoped to treat inflammation with fewer side effects.
Why are COX2 inhibitors not recommended for long-term use despite their potential benefits in reducing inflammation?
Although COX2 inhibitors target the enzyme responsible for producing inflammatory prostaglandins and were designed to have fewer side effects than traditional NSAIDs, studies have shown that some patients who take these drugs have an increased risk of heart attacks and strokes, leading to the recommendation against long-term use.
Besides eicosanoids, what other lipid signal molecules are involved in regulating inflammation and other cellular processes?
Sphingolipids also act as extracellular signals to help regulate inflammation, cell adhesion and migration, and cell growth and death. Like eicosanoids, sphingolipids combine with G protein-coupled receptors in the membranes of their target cells.
Explain the concept of agonists and antagonists in receptor-ligand interactions.
When a ligand binds to a receptor, it can either activate the receptor and elicit a response (agonist) or occupy the binding site and prevent the receptor from responding (antagonist). Agonists compete with the primary ligand for binding sites and elicit a response, while antagonists block receptor activity.
