Cell Signaling and GPCRs Overview

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Questions and Answers

What is a primary function of Ca2+ ions in cell signaling?

They lead to the permanent activation of all signaling proteins.

They only function in neurotransmitter release.

They inhibit all forms of signaling.

They act as a secondary messenger to mediate signaling pathways. (correct)

Which receptor type is primarily linked to the activation of adenylyl cyclase?

Nuclear hormone receptors

G-Protein Coupled Receptors (correct)

Ionotropic receptors

Receptor Tyrosine Kinases

What role do phosphatidylserine and diacylglycerol (DAG) play in cell signaling?

They initiate muscle contractions directly.

They serve as secondary messengers that modulate protein kinase activity. (correct)

They are involved in the digestion of nutrients.

They function solely as structural components of cell membranes.

What is the significance of Ca2+ oscillations in signaling pathways?

They enable temporal signaling and can influence different cellular responses. Signup and view all the answers

How do G-protein linked receptors contribute to neurotransmitter signaling in olfaction?

They activate downstream signaling cascades that result in the perception of smells. Signup and view all the answers

What is the primary function of CaM-kinase II in neuronal cells?

To act as a frequency decoder for Ca2+ oscillations Signup and view all the answers

Which of the following statements about olfactory receptors is accurate?

Each type of olfactory receptor can detect a wide array of odorants. Signup and view all the answers

How do G-protein coupled receptors (GPCRs) regulate physiological tasks?

By activating trimeric G-proteins that influence adenyl cyclase and PLC-b Signup and view all the answers

Which second messenger is NOT associated with G-protein signaling pathways?

NADH Signup and view all the answers

What process is mediated by the activation of olfactory receptors when an odorant is detected?

Formation of cAMP Signup and view all the answers

What role do RGS proteins play in G-protein signaling?

They turn off G-proteins by acting as GAPs Signup and view all the answers

Which of the following accurately describes the role of Ca2+ in cellular signaling?

Ca2+ functions as a second messenger for signal amplification. Signup and view all the answers

What is the primary function of the signal amplification mechanism in GPCR pathways?

To enhance and prolong the signaling response Signup and view all the answers

What role do intracellular signaling proteins play in signal amplification?

They act as molecular switches to enhance sensitivity to signal strength. Signup and view all the answers

Which domain specifically binds phosphorylated tyrosine within signaling proteins?

SH2 domain Signup and view all the answers

What is created during the clustering of receptors and signaling proteins?

A concentrated signaling microenvironment. Signup and view all the answers

How do second messengers affect intracellular signaling?

They are generated in large numbers and diffuse rapidly. Signup and view all the answers

What is a characteristic of G-protein linked receptors in signal transduction?

They can interact with different types of intracellular proteins. Signup and view all the answers

What is a key feature of calcium signaling in cellular responses?

It is characterized by oscillations in calcium concentration. Signup and view all the answers

What type of neurotransmitter signaling is particularly relevant in olfaction?

Signal transduction involving synaptic connections with low-affinity receptors. Signup and view all the answers

What do Ca2+ oscillations indicate in cellular signaling processes?

They represent a modulation of signaling pathways through variations in calcium levels. Signup and view all the answers

Study Notes

Cell Signaling Overview

Cell-cell signaling is ancient, varied, and cooperative. It's integral to cell context, second messengers, molecular switches, cascade amplification, and keeping/turning pathways off.
There are over 1500 receptors in humans.
Signaling molecules can be proteins, peptides, amino acids, nucleotides, steroids, retinoids, dissolved gases (like NO), light, touch, and heat. These are often released through exocytosis or transmembrane transport.

G-Protein Coupled Receptors (GPCRs)

GPCRs are a large family of receptors, comprised of trimeric G proteins.
They regulate the turning off of G proteins, adenylyl cyclase/cAMP, PKA, IP3, phospholipase C-β, Ca2+ mediated signaling, and CaM-Kinase. Olfaction is also related to GPCRs.

Bacterial Films

K+ efflux changes transmembrane voltage and releases K+ ions in neighboring cells.
Available glutamate and Yugo are involved in biofilm processes.
B. subtilis is a pertinent example/species involved in bacterial films

cAMP in Dictyostelium discoideum

Dictyostelium discoideum uses cAMP for fruiting body formation, spore germination, starvation, and aggregation.
The signal transduction pathways used by Dictyostelium for chemotaxis and leukocyte migration to infection sites are conserved.

Origins of Signaling

Cell signaling is ancient. Our current systems likely evolved from unicellular ancestors.
Examples of signaling systems in unicellular organisms include those seen in S. cerevisiae, such as mating factor peptides.

Cell Signaling: Reception

Receptors are located on the plasma membrane or inside the cell (intracellular receptors).
Hydrophilic signals bind to cell-surface receptors.
Hydrophobic signals bind to intracellular receptors.

Types of signaling

Short range: Contact-dependent, immune system, etc.
Long range: Synaptic neurotransmitters, endocrine hormones, etc.
Autocrine: Signals target the same cell that released them.
Paracrine: Signal targets neighboring cells.
Endocrine: Signals travel through the bloodstream to distant targets.

Nitric Oxide

Nitric oxide (NO gas) mediates smooth muscle relaxation.
NO can increase blood flow by up to 200%, reducing blood pressure
NO has a 5-10 sec half-life and is rapidly diffusible across membranes.

Steroid and Thyroid Hormones

Steroid and thyroid hormones are small and hydrophobic, remaining in blood for hours or days.
These hormones often bind to nuclear hormone receptors, which are receptors and effectors at the same time.
Humans have approximately 48 nuclear hormone receptors.

Receptor Classification

Receptors can be divided into Cell-surface receptors and Intracellular receptors.

Signal Transduction Pathways

Speed of signal is important. Some pathways (e.g. enzyme activation) take less than a second to minutes, others, (e.g. transcriptional regulation) take minutes to hours.
Some signals have a fast effect and some have a slow effect. Signals can have many different consequences, some fast and some slower.
This is different from the speed at which the signal is received and interpreted by the cell.

GPCRs

*G-protein-coupled receptors—*are a large family of receptors that span the plasma membrane seven times. They mediate many physiological tasks and are activated by various molecules like hormones, photons, neurotransmitters, peptides, derivatives of amino acids, nucleotides, and fatty acids.
GPCRs are important in many pathological conditions and are targets for about 25-30% of drugs.
GPCRs are important in many physiological processes (smell, taste, vision, immune response, etc.)
GPCRs often use intracellular signaling proteins and second messengers.

G Proteins

G proteins are functionally coupled receptors to enzyme and/or channel effectors.
G proteins are molecular switches. Turning "on" and "off"
G proteins can be grouped into 5 main groups.

Regulation of Signal Pathway Activation/Deactivation

Pathways are regulated by the presence/absence of ligands to turn themselves on and off.
Important for cell desensitization—can happen at all steps in signal transduction pathways
Hedgehog pathway is shown as an example of how pathways can be tightly regulated.

Important Second Messengers

cAMP is frequently produced by adenylyl cyclase. cAMP activates PKA.
IP3 is usually produced by activation of phospholipase C. IP3 releases calcium from the endoplasmic reticulum
DAG is produced with IP3, it stays in the membrane and may activate PKC.
Calcium moves from the outside to the cytoplasm.

Important Signaling Proteins

Many proteins are involved in signal transduction, including:

kinases,
phosphatases,
scaffolding proteins,
G-proteins,
transcription factors, and
others.

Examples/Applications of Cellular Processes

Cholera toxin, a bacterial toxin, locks Gs α-subunit in the active state, causing high levels of cAMP and resulting in dehydration.
CFTR is critical for water movement in lungs and gut, and important for preventing bacterial growth. Mutations in CFTR can cause cystic fibrosis.
Olfactory receptors (in the nasal epithelium) detect odorants, and this activates cAMP production.

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Description

Explore the intricate world of cell signaling, focusing on cell-cell communication, GPCRs, and their role in various biological processes. This quiz covers the diverse types of signaling molecules and the significance of bacterial films in signaling pathways. Test your understanding of these fundamental concepts in cellular biology.