Cell Bio Final

Why does nitric oxide (NO) act as a paracrine signal only on nearby cells?

NO reacts quickly with water and oxygen in the surrounding area, limiting its ability to travel far and restricting its effects to nearby cells.

How do the general structures of GPCRs and enzyme-coupled receptors (e.g., receptor-tyrosine kinases, RTKs) differ?

GPCRs are transmembrane proteins with a single polypeptide chain that threads through the lipid bilayer seven times. Enzyme-coupled receptors (like RTKs) also span the membrane but have intrinsic enzymatic activity or interact with a dimer-forming signaling protein that acts as an enzyme, typically initiating phosphorylation cascades.

How does the binding of a signal molecule activate receptor-tyrosine kinases (RTKs) to trigger the assembly of an intracellular signaling complex?

The signal molecule (ligand) binds to the RTK, causing it to dimerize. This dimerization activates the receptor, leading to autophosphorylation of tyrosine residues in the receptor’s intracellular domain. These phosphorylated tyrosines serve as docking sites for intracellular signaling proteins, initiating downstream signaling pathways.

List several intracellular signaling proteins activated by RTKs.

phospholipase C and Ras

Outline how RTKs activate the MAP kinase signaling module.

the RTK will activate Ras which then phosphorylates a MAP-kinase signalling module

Indicate how Ras can fuel uncontrolled proliferation in cancer.

There is a mutation that shuts off the GTPase activity of Ras which thus won't allow it to shut off promoting uncontrolled cell proliferation

Review how extracellular signals that promote cell growth and survival activate PI-3-kinase signaling pathways.

Phosphorylates inositol phospholipids, and they then serve as docking sites for signalling proteins in the cytosol where they can interact with each other

How does Akt promote cell survival via Bad and stimulate cell growth via Tor?

Akt promotes cell survival by inactivating Bad, a protein that would otherwise cause cell death. When Akt inactivates Bad, it helps the cell survive. Simultaneously, Akt stimulates cell growth by activating the Tor system, which encourages the cell to grow and divide.

What is the main difference between cell signaling in plants and animals?

Plant signaling mainly relies on hormones and plasmodesmata, while animal signaling involves the use of neurons and the circulatory system for faster, long-distance communication.

How does the ethylene signaling pathway regulate transcription in plants?

When ethylene binds to its receptors, it triggers a signaling cascade that activates or deactivates specific transcription factors, which in turn regulate gene expression to help the plant respond to ethylene.

Explain how multiple signaling pathways can integrate information to produce a coordinated cell response.

Integration occurs when different signaling pathways connect and interact. This allows the cell to combine multiple signals and respond to a variety of inputs.

What are the four main types of extracellular signal molecules based on how they are delivered?

Endocrine, Paracrine, Neuronal, and Contact-dependent signaling.

What is endocrine signaling?

A type of signaling where hormones are released into the bloodstream by endocrine cells (e.g., in the pancreas) to send signals throughout the body.

What is paracrine signaling?

A form of local signaling where signal molecules diffuse through extracellular fluid and affect nearby cells.

What is neuronal signaling?

A fast and specific signaling method where nerve cells use neurotransmitters to communicate with target cells.

What is contact-dependent signaling?

A form of signaling where cells must be in direct contact, often used to help cells specialize into different types.

What types of receptors do extracellular signal molecules bind to?

They bind to cell-surface receptors or intracellular receptors, depending on the molecule's size and solubility.

What determines a cell’s response to a signal molecule?

The specific signaling molecules it produces and how those molecules change effector proteins.

What do effector proteins do in a cell?

They directly affect the cell’s behavior in response to a signal.

Why can the same signal molecule cause different responses in different cells?

Because different target cells have unique combinations of receptors and signaling pathways.

What causes rapid cell responses to a signal?

Activation of proteins that are already present in the cell.

Why do some cell responses take minutes or hours?

Because they require changes in gene expression and the production of new proteins.

Give examples of slow cell responses.

Cell growth and cell division.

What are the three main classes of cell-surface receptors?

Ion-channel-coupled receptors, G-protein-coupled receptors (GPCRs), and enzyme-coupled receptors.

What is the function of ion-channel-coupled receptors?

They change membrane permeability to certain ions, altering the membrane potential and possibly generating an electrical current.

What do G-protein-coupled receptors (GPCRs) do when activated?

They activate G-proteins that switch enzymes or ion channels on or off, initiating an intracellular signaling cascade.

What is the role of enzyme-coupled receptors?

They either act as enzymes or associate with enzymes to activate signaling pathways inside the cell.

How does phosphorylation act as a molecular switch?

Phosphorylation turns proteins on or off by adding or removing a phosphate group, changing the protein’s activity.

What type of enzyme adds a phosphate group to a protein?

A protein kinase.

What type of enzyme removes a phosphate group from a protein?

A protein phosphatase.

What determines whether a protein is active or inactive in phosphorylation signaling?

The balance between kinase and phosphatase activity.

What are two examples of protein kinases?

Serine/threonine kinases and tyrosine kinases.

What type of signaling do ion-channel-coupled receptors carry out?

They convert chemical signals into electrical signals by opening ion channels.

Where are ion-channel-coupled receptors especially important?

In the nervous system, for fast signal transmission across synapses.

What happens when a neurotransmitter binds to an ion-channel-coupled receptor?

The ion channel opens, allowing specific ions to pass through the membrane.

What does the opening of ion channels change in the target cell?

It changes the voltage across the membrane (membrane potential).

What are some example ions that pass through these channels?

Sodium (Na⁺), potassium (K⁺), and calcium (Ca²⁺).

What types of substances commonly interact with cell-surface receptors?

Substances like heroin, nicotine, tranquilizers, and chili peppers.

How do substances like heroin and nicotine affect cell-surface receptors?

They can block or overstimulate the receptor's normal activity.

What is the effect of overstimulation or blockage of cell-surface receptors?

It alters normal physiological processes, often leading to changes in behavior or health.

How do many drugs and poisons affect cell-surface receptors?

They interact with receptors to either block or overstimulate their normal function, affecting cell signaling.

What happens when glucose levels increase in pancreatic beta cells?

Increased glucose leads to more ATP production, which causes potassium (K⁺) channels to close.

What is the effect of potassium channel closure in pancreatic beta cells?

The closure of potassium channels causes depolarization of the cell membrane.

What happens after depolarization in pancreatic beta cells?

Depolarization opens calcium (Ca²⁺) channels, allowing calcium ions to enter the cell.

What is the role of calcium influx in pancreatic beta cells?

The influx of calcium triggers insulin release from the beta cells.

How do GPCRs contribute to signal transduction in pancreatic beta cells?

GPCRs help regulate various cellular processes involved in signal transduction, including those affecting glucose metabolism and insulin secretion.

What is the structure of a G-protein-coupled receptor (GPCR)?

GPCRs consist of a single polypeptide chain that threads back and forth across the lipid bilayer seven times.

Where do extracellular signal molecules bind to a GPCR?

Extracellular signal molecules bind to the GPCR on the extracellular side of the membrane.

What types of signal molecules typically bind to GPCRs?

Various types of extracellular signal molecules bind to GPCRs, including hormones, neurotransmitters, and sensory signals (e.g., light, odorants).

What happens when a signal molecule binds to a GPCR?

Binding of a signal molecule to a GPCR causes a conformational change in the receptor, which activates the associated G-protein and initiates intracellular signaling pathways.

What is the general structure of a G protein?

A G protein is composed of three subunits: alpha (α), beta (β), and gamma (γ).

What happens when a G protein is activated by a GPCR?

When a GPCR is activated, the G protein undergoes a conformational change. This leads to the dissociation of the beta-gamma (βγ) subunits from the alpha (α) subunit.

What is the role of the G protein’s subunits after activation?

After activation, the alpha subunit typically binds GTP and interacts with target proteins to propagate the signal. The beta-gamma subunit can also activate other target proteins, such as ion channels or enzymes.

What are the two main classes of enzymes targeted by G proteins?

• Adenylyl cyclase

• Phospholipase C (PLC)

What second messenger does adenylyl cyclase produce?

cyclic AMP (cAMP).

What second messengers does phospholipase C (PLC) produce?

inositol trisphosphate (IP₃) and diacylglycerol (DAG).

How does inositol trisphosphate (IP₃) affect the cell?

IP₃ increases Ca²⁺ levels in the cell, which helps propagate the signal.

What is the role of second messengers like cAMP, IP₃, and DAG in signaling?

spread quickly within the cell, amplifying the signal and triggering specific cellular responses.

How is cyclic AMP (cAMP) produced in response to G protein activation?

The activated G protein alpha subunit activates adenylyl cyclase, which converts ATP into cyclic AMP (cAMP).

How is the signal terminated after cAMP production?

The enzyme cAMP phosphodiesterase breaks down cAMP into AMP, terminating the signal.

How does caffeine affect cAMP levels in the nervous system?

caffeine inhibits cAMP phosphodiesterase, preventing the breakdown of cAMP and keeping cAMP levels high, which enhances signaling.

Where is phospholipase C (PLC) activated in GPCR signaling, and what does it do?

In GPCR signaling, phospholipase C (PLC) is activated and cleaves a membrane lipid to produce diacylglycerol (DAG) and inositol trisphosphate (IP₃).

What are the second messenger molecules produced by PLC activation, and what do they do?

The second messenger molecules produced by PLC activation are DAG, IP₃, and Ca²⁺. These help propagate the signal inside the cell.

What are the two sources of calcium ions (Ca²⁺) in cell signaling?

The two sources of calcium ions (Ca²⁺) are internal Ca²⁺ stores (such as the endoplasmic reticulum) and external Ca²⁺ that enters the cell.

How is internal calcium (Ca²⁺) released during signaling?

Internal calcium (Ca²⁺) is released through the activation of inositol trisphosphate (IP₃), which binds to receptors on the endoplasmic reticulum (ER), triggering the release of Ca²⁺.

What is the structure of the IP₃ receptor and how does it function?

The IP₃ receptor is a homotetramer (a protein complex with four subunits) and has four binding sites for IP₃. When IP₃ binds, it triggers the release of Ca²⁺ from the ER.

What biological process is triggered by calcium ions in muscle cells?

Muscle contraction is triggered by calcium ions in muscle cells.

How do calcium ions affect neurotransmitter release?

Calcium ions trigger synaptic vesicle release, facilitating neurotransmitter release in neurons.

What role do calcium ions play in signal transduction pathways?

Calcium ions activate kinases in signal transduction pathways, which further propagate the signal inside the cell.

How do calcium ions affect gene expression?

Calcium ions help regulate gene expression by influencing transcription factors and other proteins involved in the process.

What enzymes can be activated by calcium ions?

Calcium ions can activate enzymes like phosphatases, which are involved in cellular processes like dephosphorylation.

How do calcium ions regulate cell division and growth?

Calcium ions play a role in regulating cell division and growth by affecting signaling pathways that control the cell cycle.

How do cells keep the concentration of calcium ions low in the cytosol?

Cells keep calcium ion (Ca²⁺) levels low in the cytosol by using calcium pumps (e.g., Ca²⁺-ATPase pumps).

What is the role of calcium pumps in regulating cytosolic Ca²⁺ levels?

Calcium pumps move Ca²⁺ out of the cytosol and into the extracellular space or internal stores like the endoplasmic reticulum (ER) or mitochondria.

How do cells terminate a calcium ion signal?

Cells terminate a calcium ion signal by using calcium pumps to actively transport Ca²⁺ back into the ER or out of the cell.

What role do calcium-binding proteins like calmodulin play in terminating a calcium ion signal?

Calcium-binding proteins such as calmodulin help buffer cytosolic calcium, reducing the free Ca²⁺ concentration and helping terminate the signal.

How do enzymes like phosphatases help terminate a calcium ion signal?

Phosphatases deactivate components in the signaling pathway, effectively stopping the signaling cascade.

How does calcium (Ca²⁺) stimulate the production of nitric oxide (NO) in smooth muscle cells?

Ca²⁺ stimulates NO synthase, which produces NO from arginine.

What happens after nitric oxide (NO) is produced in smooth muscle cells?

NO diffuses into adjacent smooth muscle cells in the cell wall, leading to relaxation of the muscle cells.

What is the outcome of nitric oxide (NO) triggering the relaxation of smooth muscle cells?

The relaxation of smooth muscle cells causes vasodilation, leading to increased blood flow.

What is the purpose of creating mutant RTKs with tyrosine-to-phenylalanine mutations?

To prevent phosphorylation at specific tyrosine residues and identify which tyrosines are docking sites for intracellular signaling proteins.

What happens when you activate a mutant RTK with tyrosine mutations?

The RTK activates, but specific intracellular signaling proteins may fail to bind, revealing which tyrosines are important for docking.

How can you identify which tyrosines are docking sites for signaling proteins?

By observing which signaling proteins fail to bind to the mutant RTK with tyrosine mutations. The loss of binding indicates the mutated tyrosine was a docking site.

How can mapping mutant RTKs with different tyrosine mutations help with understanding signaling pathways?

Testing multiple mutants allows you to map specific tyrosines to their downstream signaling partners, identifying key docking sites for signal propagation.

What is a common amino acid substitution used in mutant RTKs to prevent phosphorylation at tyrosine residues?

Phenylalanine (Y → F) is commonly used to replace tyrosine residues in mutant RTKs.

What is the role of mutant cell lines in studying signaling pathways?

Mutant cell lines are used to introduce changes in key proteins to study how these alterations affect downstream signaling and to identify proteins involved in the pathway.

How does overactive Ras help dissect signaling pathways?

Overactive Ras helps identify which signaling proteins are involved in the pathway by activating the signaling cascade continuously, allowing researchers to observe the effects on the pathway.

What is the purpose of introducing mutant forms of Ras in research?

Mutant Ras forms allow researchers to study how mutations affect signaling pathways and which proteins are essential for proper signaling.

How do researchers determine the role of specific proteins in a signaling pathway using mutant cell lines?

By introducing mutations in specific proteins, researchers can observe which proteins are required for proper signaling and how they contribute to the pathway's function.

What is the role of the epidermis in the skin?

the outermost layer of the skin, consisting of flat, dead cells that provide a protective barrier against environmental damage.

What makes up the dermis, and what is its function?

tough layer beneath the epidermis composed of connective tissue, blood vessels, and nerves. It provides structural support, nourishment, and sensation to the skin.

What is the function of the hypodermis in the skin?

deepest layer of skin, made up of connective tissue and fat. It insulates the body, stores energy, and connects the skin to underlying muscles and bones.

How does cell replacement occur in the skin epidermis?

In the skin epidermis, stem and precursor cells are located in the basal layer, attached to the basal lamina. These cells divide and differentiate to replace the outer layers of skin cells, which are shed regularly.

How does cell replacement occur in the intestinal epithelium?

In the intestinal epithelium, the absorptive and secretory cells form a single-layer epithelium covering villi. Stem cells at the base of crypts continuously divide, giving rise to new cells that migrate upwards to replace older cells.

What is the function of hematopoietic stem cells (HSCs)?

Hematopoietic stem cells (HSCs) are responsible for producing all types of blood cells, including red blood cells, white blood cells, and platelets, through the process of hematopoiesis.

How do signaling mechanisms maintain the stem-cell system in the intestine?

Wnt signaling promotes the proliferation of stem cells and precursor cells in the intestinal crypts, ensuring the continuous renewal of the intestinal epithelium.

What are the three main processes involved in tumor development?

• Increased Cell Proliferation: Tumor cells divide uncontrollably.

• Resistance to Apoptosis: Cancer cells avoid programmed cell death.

• Invasion and Metastasis: Tumor cells spread to other tissues and organs.

What are the four main cancer-critical mutations?

• Oncogene Activation: A proto-oncogene is mutated into an oncogene, promoting excessive growth.

• Loss of Tumor Suppressors: Mutations inactivate tumor suppressor genes, removing growth control.

• DNA Repair Defects: Faulty DNA repair genes lead to genomic instability.

• Telomerase Activation: Reactivation of telomerase allows unlimited cell division.

Why is cancer most often a disease of old age?

Cancer is more common in older people because mutations accumulate over time, DNA repair becomes less efficient, and immune surveillance weakens, increasing cancer risk.