unit 5 - cell communication Flashcards
gap junctions
connect the cytoplasm of neighboring cells and allow passage of ions and small molecules between them. allows coordination of tissues (like cardiac muscle contraction)
contact cell-cell signalling
signal is made through physical contact of signal and receptor molecules (glycoproteins and glycolipids) connecting on the 2 cells’ surfaces
examples:
- contact inhibition (cells dividing for growth or to heal wounds know to stop dividing when they touch another cell—means gap is filled)
- cortical reaction (egg builds wall to prevent multiple sperm from penetrating after the first sperm signal-touches)
- phagocytic cells recognize foreign microbes and form pseudopods to eat them
- cell specialization during embryonic development
contact inhibition
mechanism of cell-cell signaling that is important in wound healing. cells divide in the absence of a cell-cell signal (gaps from damaged cells), and stop dividing when they come in contact with each other again
paracrine signal
uses secretory molecules
“para” = nearby - signal molecules travel short distances
examples:
- immune cells and regulation of inflammation
- growth factors that regulate formation of blood cells from stem cells
- synaptic signalling
autocrine signal
uses secretory molecules that bind to the outside of the same cell to trigger a reaction
examples:
- T cells in the immune system produce antigens to trigger their proliferation
- abnormal signalling can lead to the uncontrolled growth of cancer cells
synaptic signal
uses secretory molecules
type of paracrine signalling, but specifically involving electrical signals in neurons
endocrine signal
uses secretory molecules called hormones, come from endocrine glands
long-distance transport via blood and circulatory system
what does the Delta signal do?
controls nerve cell differentiation in flies. touch receptor.
when a cell specializes as a neuron, it has Delta signal protein in the membrane. when this connects with the Notch receptor protein ona
neighboring cell, the Notch tail is cleaved and migrates to the nucleus to regulate appropriate gene transcription, preventing neighboring cells from also becoming neurons
types of protein kinases
- serine/threonine kinases: phosphorylate proteins on serine or threonine amino acids
- tyrosine kinases: phosphorylate kinases on tyrosine amino acids
G-proteins
proteins activated using GTP
* GTP: active
* GDP: inactive
*have intrinsic GTP-hydrolyzing (GTPase) activity–can regulated themselves
G-protein-coupled receptors (GPCRs)
- found in plasma membrane
- evolutionarily old, found in bacteria also
- 1 polypeptide, spans plasma membrane 7x (7 membrane-spanning alpha-helices), large extracellular domain that binds the hormone
- after the signal binds, the receptor undergoes a conformational change to attract and activate a G-protein in the cytosol
- conformational change of alpha subunit, GDP disassociates and is replaced with GTP
- activated alpha subunit separates from activated beta-gamma subunit
- both activated subunits can then regulate target proteins/enzymes by activating them. target proteins act as secondary messengers and carry on the signalling cascade
receptor protein-tyrosine kinase (RTKs)
transmembrane proteins that form dimers when activated, cytoplasmic domains act as enzymes that activate other proteins
* extracellular molecule bonds to a receptor, RTKs dimerize
* dimers autophosphorylate (one half adds phosphate groups to the tyrosine residue of the other half) becomes activated
* proteins with SH2 domains can recognize and dock at specific phosphotyrosine residues
* proteins are phosphorylated and propagate the signal further
GPCR interference
- cholera: cholera toxin modifies alpha subunit of G-protein so it can’t hydrolyze its GTP and is perpetually active and opens too many Cl- channels, leading to diarrhea, dehydration, and death
- whooping cough: pertussis toxin lock the alpha subunit of a G-protein in inactive, GDP-bound state. Prolonged signal that stimulates coughing, interferes with normal functioning
- drugs used in treatment of nearly every major organ system
- anti-clotting, high blood pressure, asthma, mental health medications
adenylyl cyclase
membrane-bound enzyme that produces cAMP using ATP
* activated by the activated alpha subunit of a G-protein
second messengers
small, water soluble molecules/ions that diffuse through the cell and relay an extracellular signal to the interior of the cell
* most common: cAMP and IP3/Ca2+
protein kinase A
enzyme that uses ATP to phosphorylate proteins, including transcription factors in the nucleus to regulate gene expression
* 4 subunits, 2 regulatory and 2 catalytic
* activated by cAMP, which binds to the regulatory subunits
* catalytic subunits can detach and enter the nucleus
IP3 and DAG
second messenger molecules that help activate protein kinase C
products of PIP2, a type of phospholipid in the cell membrane
produced when:
1. activated alpha-subunit of a G-protein activates phospholipase C-beta
2. phospholipase C-beta phosphorylates and hydrolyzes PIP2 into two molecules, IP3 and DAG
- IP3 is
main functions of cAMP
- activating protein kinase A
- activating gene transcription
calmodulin
- most common Ca2+ responsive protein, present in the cytosol of all eukaryotic cells
- dumbell shape- two globular ends and a long flexible alpha-helix. 2 Ca binding sites
- Ca2+ binds, calmodulin changes conformation and wraps around various target proteins to regulate their activity
-Ca2+/calmodulin-dependent protein kinases, usually control gene transcription
signals that can bind intracellular receptors
steroid and thyroid hormones
* cortisol, estradiol, testosterone, thyroxine
dissolved gases, only act locally
* nitric oxide
malfunctioning receptor in sex determination
androgen sensitivity syndrome
* SRY gene on Y chromosome produces testes which produce testosterone
* AR gene contains the testosterone receptor. if mutated, body develops testes but female sex characteristics despite XY chromosomes
function of NO as a molecular signal
induces vasodilation to increase blood flow
* nerve cells secrete acetylcholine that binds to GPCRs in endothelial cells on the interior of blood vessels, stimulating arginine residues to produce nitric oxide
* NO diffuses out of endothelial cells into smooth muscle cells with NO receptors, which relax in response
guess which silly little pill uses nitric oxide……..to increase blood flow……
three chemical classes of hormones
- lipid/steriod hormones - bind intracellular receptors in the cytosol or nucleus
- gas (NO) - diffuses across plasma membrane, major paracrine signaling molecule in circulatory system
- peptides and protein hormones - bind to extracellular receptors, the widest variety of signaling molecules
Signaling by the steroid hormone estrogen is an example of _______ signaling
endocrine
When activated, T lymphocytes secrete chemical factors that lead to their own growth and proliferation. This is an example of _______ signaling.
autocrine
Which signal molecule diffuses through the plasma membrane to ultimately bind nuclear receptors and influence transcription?
estrogen
Steroid hormones usually act via receptors that…
bind to DNA. they act as transcription regulators
Nitric oxide is a signal molecule that can
diffuse across cell membranes and directly alter the activity of intracellular enzymes.
The medical usage of nitroglycerine in heart disease is based on its
conversion to NO, which stimulates blood vessel dilation. treats patients with angina.
The G protein that activates adenylyl cyclase is a
heterotrimeric G protein that separates into a and βγ subunits
Cholera toxin inhibits the ability of the a subunit of G protein to split GTP. If you treated cells with cholera toxin, the resulting effect would be _______ of adenylyl cyclase
stimulation
A major function of cAMP in animal cells is to activate
protein kinase A
During the odorant response in the cilia of olfactory neurons, the second messenger _______, leads to the opening of ion channels in the plasma membrane of olfactory neurons and the production of a nerve impulse.
cAMP
MAP kinase is an abbreviation for _______ protein kinase.
mitogen-activated
Ras is a membrane-bound _______ when activated.
G-protein that binds GTP
Hydrolysis of PIP2 by phospholipase C produces:
DAG and IP3
G protein-coupled receptors are important molecules involved in signal transduction. Which statement about G protein-coupled receptors is true?
They generally contain seven membrane-spanning a helices.
Which statement about G protein signaling is false?
The a subunit becomes deactivated when the hormone dissociates from the receptor.
Cyclic AMP (cAMP) is synthesized from ATP by the action of
adenylyl cyclase
Receptor tyrosine kinases represent critical molecules involved in growth and differentiation though phosphorylation of target substrates on tyrosine residues. Which structural feature is not common among all receptor tyrosine kinases?
a single polypeptide
Which of the following is not a commonly observed consequence of the binding of a signaling molecule to its cell surface receptor?
increased synthesis of the receptor
second messengers are:
small molecules and ions that relay signals received by cell-surface receptors
SH2 domains are:
protein domains that bind phosphotyrosine-containing peptides
mechanism of viagra
blocks enzyme that degrades cGMP.
NO enters endothelial cells of penis blood vessels, activating guanylyl cyclase to convert GTP to cGMP, which activates PK-G and induces vasodilation
continuous activation of PK-G
types of cell responses
- Control the behavior of the cell
- Opening or closing ion channels (send an action potential)
- Altering cell metabolism (activate or inhibit metabolic enzymes)
- Altering gene expression (turning on or off genes)
- Altering shape and movement
- Cell division
- Cell differentiation
mutations that lead to cancer
- abnormal autocrine signaling that produces continuous growth factors
- overexpression of RTKs, spontaneous dimerization in the absence of growth signals, covalent linkages of the extracellular or tyrosine kinase domains that lead to perpetually dimerized receptors
- production by cancer cells of dimerized proteins with tyrosine-kinase function
- mutated Ras proteins can lead to uncontrolled cell division - activated MAP kinase
how do steroid hormones regulate transcription?
bind intracellular receptors, then the receptor-hormone complex enters the nucleus and regulates gene activity by binding to regions of DNA and altering their level of transcription
- each hormone binds a different receptor protein and each receptor acts at a specific regulatory site in the DNA
example of dysfunction: intersex individuals that lack the receptors to express genes activated by testosterone
how do signal transduction pathways work?
binding of a signalling molecule activates receptors –> receptors activate enzymes –> enzymes release second messengers –> protein producing the target cellular response is activated
Ras proteins
- small GTP-binding protein, similar to alpha subunit of G-proteins, found on cytoplasmic side of the plasma membrane
- activated by receptor tyrosine kinase, via an adaptor protein with an SH2 domain
- promotes activation of phosphorylation cascade using Mitogen-activating protein kinases (MAP-kinase)
- eventually alters gene trascription to stimulate cell proliferation, apoptosis inhibition, or cell differentiation
mutated Ras proteins
- inhibited removal of GTP
- perpetually active Ras leads to uncontrolled cell division (cancer)
Akt protein kinase
- activated by PIP3
- causes a phosphorylation cascade that inhibits apoptosis
structure and mechanism of intracellular receptor gene transcription regulation
structure: transcription activating domain, DNA binding domain, signal molecule binding domain
- in its inactive form, intracellular receptors are bound to an inhibitor protein that prevents the DNA-binding domain from interacting with DNA
- lipid-soluble signal molecule (steroid hormones) binds to an intracellular receptor, causing the inhibitor to dissacociate and expose the DNA binding site
- hormone-receptor complex moves into the nucleus and binds DNA to regulate transcription
