Signal Transduction in Biology

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Questions and Answers

What initiates the change in cellular activity via GPCRs?

GTP hydrolysis

GDP release from an effector

Agonist binding to the receptor (correct)

Dissociation of the G protein complex

What is the primary role of the G protein in GPCR signaling?

To bind the agonist

To hydrolyze GTP

To synthesize second messengers

To interact with effectors (correct)

Which subunit of the G protein is primarily responsible for interacting with GTP?

Gamma subunit

Alpha subunit (correct)

Beta subunit

Heterotrimeric subunit

What happens after the GTP is hydrolyzed to GDP in the GPCR signaling pathway?

The alpha and beta-gamma subunits reform the heterotrimer Signup and view all the answers

How many possible combinations of G proteins can be formed from the human genome?

Over 1000 Signup and view all the answers

What characterizes the GPCRs and G protein interaction?

It activates the G protein through GTP-GDP exchange Signup and view all the answers

What is the function of second messenger-generating enzymes activated by GPCRs?

To amplify the cellular response Signup and view all the answers

Which statement about GPCRs is true?

GPCRs have a shared basic structure. Signup and view all the answers

What initiates the 'on' state of G proteins?

GDP/GTP exchange facilitated by receptors Signup and view all the answers

What serves as the timer/off switch for G proteins?

GTP hydrolysis duration Signup and view all the answers

Which G protein pathway decreases cAMP levels?

Gi pathway Signup and view all the answers

Which condition is caused by a gain-of-function mutation?

Familial male precocious puberty Signup and view all the answers

How does Cholera Toxin (CTx) affect Gsα?

It eliminates GTPase activity. Signup and view all the answers

What is the effect of Pertussis Toxin (PTx) on Giα?

It interferes with GDP/GTP exchange. Signup and view all the answers

Which molecule is produced when Gq proteins interact with phospholipase C?

Inositol and diacylglycerol Signup and view all the answers

What role do G proteins play in cellular signaling?

They act as timers and switches. Signup and view all the answers

What is the primary function of receptors in signal transduction?

To recognize signaling molecules and evoke cellular responses Signup and view all the answers

Which type of receptor is characterized by intrinsic enzymatic activity?

Receptor tyrosine kinases Signup and view all the answers

What characterizes G protein-coupled receptors (GPCRs)?

They alter the activity of effectors such as enzymes and ions Signup and view all the answers

What initiates the signal transduction process in cells?

The binding of ligands to receptors Signup and view all the answers

Which type of receptors are typically found on cell surfaces and interact with extracellular signaling molecules?

Cell surface receptors Signup and view all the answers

What is the role of ligand binding in receptor activation?

It alters the receptor structure, initiating a response. Signup and view all the answers

What do G proteins generally require to become activated?

Ligand-receptor binding Signup and view all the answers

What is a common downstream effect once a receptor is activated?

Altered cellular functions such as contraction or secretion Signup and view all the answers

Study Notes

Signal Transduction in Biological Membranes

Signal transduction involves cells responding to extracellular molecules (e.g., hormones, neurotransmitters, growth factors) through specific receptors.
Receptors can be intracellular (e.g., steroid and thyroid hormones) or extracellular (located on the plasma membrane).
Most signaling molecules don't readily cross the plasma membrane, hence more receptors are on the cell surface.

Objectives

Understand how cells recognize signaling molecules and trigger appropriate cellular responses.
Understand how activated G protein-coupled receptors initiate a chain of signaling events involving G proteins and effector proteins (enzymes or ion channels).
The objective is further to understand how cells recognize signaling molecules to evoke a suitable cellular effect.

What is Signal Transduction?

Extracellular signaling molecules (e.g., hormones) require receptors to trigger responses in cells.
Receptors may be intracellular (e.g., for steroid hormones) or extracellular (e.g., on the plasma membrane), depending on the signal molecule.
The majority of signaling molecules don't readily cross the plasma membrane; therefore, more receptors are located at the cell surface.

Typical Signal Transduction Pathway

Signal molecules from the extracellular fluid bind to specific receptors on the plasma membrane.
The signal binding and receptor activation initiates a signaling pathway within the cell.
The pathway can trigger cellular responses like contraction, secretion, proliferation, and differentiation.

G Protein-Coupled Receptors (GPCRs)

GPCRs are a large family of cell surface receptors.
GPCRs alter the activity of effectors (enzymes, ions, or channels).
They achieve this via the activation of guanine nucleotide binding proteins (G proteins).
The GPCRs' interaction with the GPCR initiates a cascade of cellular responses.

GPCR Features

Single polypeptide chain (300-1200 amino acids).
7 transmembrane (7TM) spanning regions.
Extracellular N-terminal and intracellular C-terminal.
GPCRs number more than 700 in the human genome.

How GPCRs Cause Cellular Activity Changes

Agonist binds to the receptor.
Protein-protein interactions release GDP and bind GTP.
Released GTP interacts with effectors.
GTP hydrolyzes to GDP.
GDP reforms the heterotrimeric G protein.

G Protein Subunits and Their Function

G proteins are heterotrimeric, composed of α, β, and γ subunits.
Functional units include α and βγ subunits.
GPCR interaction activates the G protein by GTP exchange for GDP on the G protein a subunit.

α-βγ Complex Dissociation

Dissociated α-βγ complex interacts with effector proteins.
Effectors may be second messenger-generating enzymes or ion channels.
α subunit's activity eventually ceases after GTP hydrolysis back to GDP.
α-GDP and βγ subunits reform the inactive heterotrimeric complex.

G Protein Diversity

The human genome encodes multiple Gα, Gβ, and Gγ proteins.
This creates numerous possible Gα-βγ protein combinations.
Specific GPCRs preferentially interact with particular G protein types.
Extracellular signal via a specific GPCR activates a particular G protein to bring about a specific cellular response.

G Protein GTP/GDP Exchange and GTP Hydrolysis

The G protein acts as an on/off switch and timer.
GTP exchange and hydrolysis govern the duration of signal transduction effects.
The length of time taken for GTP hydrolysis is an essential aspect of signal termination.

Cellular Targets for Activated G Proteins

Activated G proteins stimulate specific intracellular targets(e.g., enzymes).
Some activated G proteins trigger specific intracellular metabolic pathways, for instance, regulating cAMP levels(adenylyl cyclase).
Other activated G proteins interact with phospholipase C to produce inositol and diacylglycerol.
Light-sensitive rhodopsin activates a G protein-mediated pathway.

GPCR Inhibition and Regulation

Some G proteins are inhibitory (Gi) and decrease cAMP levels by inhibiting adenylyl cyclase.
Inhibitory G proteins (Gq/11) interact with membrane-bound phospholipase C, generating inositol and diacylglycerol second messengers.
Photoreceptor G protein (transducing Gprotein) activates a cascade that eventually leads to hydrolyzing cyclic GMP to 5'-GMP.

Experimental Manipulation of the G Protein Cycle

Cholera toxin (CTx) eliminates G protein GTPase activity, leading to irreversible activation.
Pertussis toxin (PTx) interferes with G protein GDP/GTP exchange leading to irreversible inactivation.
Both CTx and PTx utilize ADP-ribosyl transferase for covalent modifications of specific G proteins.

Diseases Associated with Signal Transduction in GPCRs

Genetic changes in GPCRs can cause loss-of-function or gain-of-function mutations.
Examples include retinitis pigmentosa (loss-of-function in rhodopsin), nephrogenic diabetes insipidus (loss-of-function in vasopressin receptor), and familial male precocious puberty (gain-of-function in LH receptor).

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Description

This quiz explores the concept of signal transduction in biological membranes, focusing on how cells recognize and respond to extracellular signaling molecules like hormones. It covers the roles of different types of receptors, particularly G protein-coupled receptors, in initiating cellular responses. Enhance your understanding of this crucial cellular communication process.