Animal Cell Biology - Exam 4

what are the four main mechanisms of cellular communication via chemical messengers

1. autocrine signaling

2. paracrine signalling

3. endocrine signalling

4. signaling molecules not secreted (gap junctions or protein junctions)

what happens in autocrine signalling?

the cell that secretes the signal also receives the signal

what happens in paracrine signalling

1 cell produces a ligand, the ligand travels a short distance and attaches to a receptor - ligand and receptor are both proteins

what happens in endocrine signalling?

ligands circulate in the blood stream, then reach target cell some distance away. they can reach anywhere in the body

what happens in contact dependent signalling?

signalling molecule travels directly from one cell to the other - can be contact dependent (gap junctions) or juxtacrine (protein juction)

***how do organ systems, tissues, and cells communicate with one another?

cell signaling pathways/signal transduction pathways

what are the ways the next molecule in a cell signaling pathway can be activated?

phosphorylation → conformational change, enzymatic exchange (GTP ←→ GTP, ion binding

what are some of the “cellular responses” of cell signaling pathways?

affect gene expression (turn gene on or off) - regulate cell cycle; cell growth; cell survival

open/close ion channels on cell membrane

regulate metabolic pathways to synthesize biomolecules

***what are the characteristics of signaling molecules that can pennetrate the cell membrane? give three examples

small, non-ionic, hydrophobic molecules

examples: Nitric Oxide (N=O), steroid hormones, thyroid hormones

***where are receptors for signaling molecules that are small, non-ionic, and hyrdophobic?

not at the cell surface (membrane) → cytoplasmic or nuclear

***what are the traits of signaling molecules cannot penetrate the cell membrane? what are some examples?

hydrophilic (charged) or large molecules,

examples - proteins, peptides, amino acid derivatives

acetylcholine is a neurotransmitter that can elicit different cellular effects on its target cell. how can this be?

acetylcholine interacts with more than one specific type of receptor - those receptors function as different ion channels to increase membrane potential to specific ions

***where are the receptors for signaling molecules that are charged or large?

at the cell surface (membrane)

what are some examples of chemical messenger receptors that are on the cell membrane?

ion linked channel receptors

G-protein linked receptors

receptor tyrosine kinase (enzyme linked receptors)

cell contact dependent signaling

***what is nitric oxide?

gas with a free electron that can freely diffuse through the cell membrane

where is nitric oxide (NO) synthesized?

from arginine on demand

how does nitric oxide (NO) work as a signaling molecule?

there is no specific receptor for NO, but it alters the activity of intracellular target enzymes

what is one significant pathway that nitric oxide (NO) is involved in?

controlling blood pressure

how do blood vessels contract and dilate?

there is a layer of smooth muscle in the wall of blood vessels, when the smooth muscle is relaxed the blood vessel is dilated (more open), when the smooth muscle is contracted (shortens lengthwise) the blood vessel constricts (narrower)

smooth muscle contraction requires what ion?

Ca++

how does nitric oxide (NO) control blood pressure?

1. to reduce blood pressure, the parasympathetic nervous symptom releases acetylcholine (ACh), which binds to and stimulates endothelial cells of blood vessels

2. NO is synthesized in endothelial cells upon ACh stimulation

3. NO diffuses into smooth muscle cells

4. NO helps exchange GTP for cGMP

5. cGMP activates the Protein Kinase G (PKG) that inhibits Ca++ to influx to cytosol

6. intracellular [Ca++] decreases → smooth muscle relaxes → blood vessel dilates → blood pressure is decreased → blood flow is increased

!! cGMP must be degraded to allow smooth muscle to contract and regulate blood pressure/blood flow

what kind of chemical messenger are thyroxine, cortisol, aldosterone, estradiol, progesterone, and testosterone?

hormones (steroid and thyroid hormones)

what kind of effect do hormones have on organs?

slow and long lasting

what kind of receptors do steroid and thyroid hormones bind to?

intracellular receptors - penetrate the plasma membrane to bind

what kind of receptors so non-steroid hormones bind to?

membrane localalized

are steroid derivatives hydrophobic or hydrophillic?

steroid derivatives are hydrophobic

where are sex steroids secreted from?

gonads

where are corticosteroids secreted from?

adrenal glands

how is the estradiol ligand made?

cholesterol → progesterone → testosterone → estradiol

is thyroid hormone hydrophilic or hydrophobic

hydrophobic

why is thyroid hormone’s solubility special?

its an amino acid derrivative, which are typically hydrophillic, but thyroid hormone is hydrophobic

how does thyroid hormone cross the plasma membrane?

with a carrier protein

what does the structure of vitamin D₃ and retinoic acid resemble

chemical structure resembles steroid molecules

***what must the ligand do if the receptor is in the nucleus?

the ligand penetrate the plasma membrane and nuclear envelope to bind to receptor → conformational change activates receptor → activated ligand receptor-complex binds to DNA

nucleus ligand receptors in cell signaling can also work as ______

transcriptional regulators

receptors in the nucleus that also work as transcriptional regulators have a ________ binding domain and a _______binding domain

DNA, ligand

how does a transcriptional regulator ligand receptor work?

ligand penetrates plasma membrane and nuclear envelope to bind to receptor → conformational change activates receptor → activated ligand-receptor complex binds to DNA → influences gene expression by activating transcription! — Lag time to metabolic effect (metabolism just means chemical reactions in the cell)

what is the process of a steroid hormone initiating a certain cell response?

1. diffusion through membrane lipids

2. hormone enters nuclease and binds receptor

3. binding of hormone-receptor complex to DNA

4. gene activation

5. transcription and mRNA production

6. translation and protein synthesis

Target Cell Response

what effect do Heat Shock Proteins (Hsp) have on cytosolic receptors?

1. ligand-free receptor is bound to Hsp90, which keeps the receptor tethered outside the nucleus

2. upon ligand-binding, Hsp90 dissociates from the receptor allowing ligand-receptor complex to enter nucleus

3. receptor binds specific DNA sequence and recruits a transcriptional coactivator (ex: histone acetyltransferase (HAT)

in regards to heat shock proteins, when the hsitone is not acetylated, what happens to transcription?

transcription is repressed

in regards to heat shock protein, when histones are acetylated what happens to transcription?

transcription occurs

what is the primary response to the binding of a steroid hormone? what is the secondary response?

hormone-receptor complexes activate primary response genes

if the primary response protein activates a secondary response gene, secondary response proteins are synthesized

why are steroid hormones so powerful?

they can directly regulate gene expression and have widespread effects (many genes and target cells)

individual amino acids form a chain called a _________, which gets folded into structures called _______

peptide, protein

are neurotransmitters hydrophobic or hydrophillic?

neurotransmitters are hydrophillic

peptides and glycoproteins are _______, which are [HYDROPHILLIC / HYDROPHOBIC] ligands

hormones, hydrophillic

what is the most known inhibitory neurotransmitter?

GABA

when an amino acid looses it’s carboxyl group, it becomes a ________

neurotransmitter

what is the process of cell signaling via surface cell receptors

ligand binds receptor at outside surface of cell → ligand-receptor binding sets off chain of intracellular signaling events → cellular/metabolic effects

some acetylcholine receptors are also _______________

ligand gated ion channels

neurotransmitters with receptors that also act as ion channels - opening ion channels is ________

direct

neurotransmitters that cause depolarization of a post synaptic cell are ___________________

excitatory synapses

neurotransmitters that cause depolarization of a post synaptic cell are ____________________

inhibitory synapse

neurotransmission can be ________ or _________

direct, indirect

receptors can use different types of signal transmission because they have __________

diversity

is neurotransmission through G-protein-coupled receptors direct or indirect?

indirect

in indirect transmission, the receptor is NOT an ion channel, but a ______________________

transmembrane protein associated with a G protein

are peptide hormones hydrophobic or hydrophillic?

peptide hormones are hydrophillic

can peptide hormones enter the target cell?

no they cannot

what is the process of signaling through G-protein-coupled receptors & the second messenger system?

hormone binds to receptor to form the hormone receptor complex → the G-protein activates and leaves the G-protein → G protein activates adenylate cyclase → adenylate cyclase cycles ATP into cAMP → cAMP activates kinase → kinase alters enzyme activity; opens ion channels → open ion activate target cell resposne

activated enzymes catalyze ______________

metabolic reactions

GDP + P_i → GTP via _________

GEFs

GTP → GDP + P_i via __________

GAPs

a G-protein with GDP binded is [ACTIVE / INACTIVE]

inactive

a G-protein with GTP bound is [ACTIVE / INACTIVE]

active

What part of the G protein leaves the complex?

the ɑ subunit

when a ligand binds a receptor on a G-protein coupled receptor, what happens?

GEF activity activates G-protein

what does GEF stand for?

guanine exchange factor

what does GAP stand for?

GTPase activating protein

what receptor does epinepherine bind to?

G-protein coupled receptor

what is the process of epinephrine signaling through its G-protein coupled receptor?

1. epinephrine binds to the G-protein coupled receptor, the activated receptor kicks off the ɑ subunit of the G protein, which binds to and activated adenylyl cyclase

2. Adenylyl cyclase converts ATP into cAMP

3. cAMP binds to protein kinase A, phosphorylating and activating the kinase

4. Protein kinase A’s C subunis leaves and gets ATP exchanged with ADP, then the phosphate binds to a phosphorylase kinase, activating it

5. activated phosphorylase kinase activates glycogen phosphorylase, which catalyzes the breakdown of glycogen into glucose-1-phosphate, glucose is ready for glycolysis and the cell can produce ATP for energy

what is the net effect of epinepherine on a cell?

• epinephrine signaling → frees glucose to enter the blood stream for delivery to/uptake by cells that need energy → “fight or flight”

• signal amplification***

• relative speed = fast (compared to hydrophobic ligand signaling)

why is singal amplification so important?

even if ligand levels are low, can activate many enzyme molecules and produce very large effects

1 receptor-hormone complex → 3 activated G proteins → 10 activated adenylyl cyclase → 21 cAMP → 36 activated protein kinase enzymes is an example of?

signal amplification / reaction cascade

what is the most widely used second messenger?

cAMP

epinephrine adrenaline is a ____________, which is an amino acid derivative, produced/secreted by adrenal medulla

catecholamine

how can signaling through G-protein coupled receptors affect gene expression?

activated protein kinase A catalytic subunits can enter the nucleus and phosphorylate (activate) a a transcription factor called CREB (CRE-binding protein)

activated CREP binds a specific regulatory (DNA) sequence (called the CRE, cAMP response element) of target genes

regulate transcription of target genes →

effect on target cell: regulate cell division, cell survival, cell differentiation

cAMP acts as a “messenger” to relay a message from ________ the cell to ______ the cell

outside, inside

what are the first and second messengers in the second messenger system? where are they in relation to the cell?

1st messenger = the original cell messenger, outside the cell

2nd messenger = cAMP and effector molecules that will ultimately bring about the desired response within the cell

***can a hydrophobic ligand (NO, steroids, thyroid hormone) pass through the plasma membrane?

no, they cannot cross the plasma membrane

how is a hydrophobic ligand (NO, steroids, thyroid hormone) secreted from it’s cell of origin

simple diffusion/facilitated diffusion

how is a hydrophobic ligand (NO, steroids, thyroid hormone) transported in the blood stream

bound to a protein carrier (not soluble in aqueous solution)

***how does a hydrophobic ligand (NO, steroids, thyroid hormone) interact with the target cell?

crosses the cell membrane and binds to receptor in the nucleus or cytosol

***can a hydrophillic ligand (amino acid derivatives/peptides) cross the plasma membrane?

no, they cannot cross the plasma membrane

how is a hydrophillic ligand (amino acid derivatives/peptides) secreted from its cell of origin?

exocytosis → vessicles

how is a hydrophillic ligand (amino acid derivatives/peptides) transported in the blood stream?

as dissolved particles

***how does a hydrophillic ligand (amino acid derivatives/peptides) interact with its target cell?

binds to a receptor on the cell membrane

***what does a kinase do?

adds a phosphate group = phosphorylates

***what does a phosphatase do?

removes a phosphate group = dephosphoylates

the enzyme with the opposite function of a kinase is a ________

phosphotase

the enzyme with the opposite function of a phosphatase is a __________

kinase

true or false: phosphorylation always activates a protein

false: some (like Bad in the cell death pathway) are inhibited when binded to phosphate

what does a blunt arrow represent in a cell signaling pathway?

A inhibits B

in the following, increased expression of A would have what effect on B? what effect on C?

A → B → C

increased activation of B, increased activation of C

in the following, increased expression of A would have what effect on B? what effect on C?

A → B -| C

increased expression of B, decreased expression of C

in the following, increased expression of A would have what effect on B? what effect on C?

A -| B -| C

decreased expression of B, increased expression of C

in the following, increased expression of A would have what effect on B? what effect on C?

A -| B → C

decreased expression of B, decreased expression of C

what happens to a protein when a phosphate group binds? _{(not activation/inactivation, what happens to the protein itself)}

the protein changes conformation

***some cell surface receptors act as intracellular ________

enzymes

is a cell surface receptor is not acting as an intracellular enzyme, it is ___________ to an intracellular enzyme

directly linked