Lecture 5 & 6: Communication Flashcards
What are the 3 mechanisms for local signaling?
1) Gap junction dependent communication
2) Contact dependent signals
3) Paracrine and autocrine
Gap junctions are
channels that connect adjacent cells
Where are gap junctions common
Heart, Smooth muscles and some neurons
What proteins (and what structure) form the bridge between the cytoplasm of each cell
Connexin, quaternary structure
Where does the cytoplasmic bridge come from
each cell will supply a connexon to the formation of a gap junction
Hydrophobic or Hydrophilic channels forms within gap junctions
Hydrophilic
What types of solutes are able to move freely from the cytoplasm of one cell to another
small solutes
What is Contact-Dependent Signalling
A molecule (ligand) in the Extracellular matrix of one cell binds to a receptor in the membrane of the adjacent cell, or a component of the ECF surrounding the cell
Contact- Dependent signalling is important to
the immune system, axon guidance and development
Define local communication
A signaling molecule is secreted from a cell and binds to ligands either on the same cell (autocrine) or to other cells near by (paracrine)
Paracrine causes what two things
smooth muscles to dilate
increases blood flow to binded area
What are the three types of Long distance communication
1) Hormones
2) Neurotransmitters
3) Neurohormones
What is the difference between endocrine and exocrine
Endocrine = substances secreted in to blood Exocrine = substances secreted into a duct
how does hormone communication work
Hormones are secreted by endocrine glands into the blood and then find a target cell with receptor cells
Does every cell have a target for endocrine hormones
no
Define neurotransmitters
Are released from a neuron into extracellular space, travels very small distances and binds to receptors on the next target cell
Do Neurotransmitters or Endocrine system move faster
Neurotransmitters move much quicker
Define neurohormones
basically a mix of both neurotransmitters and endocrine hormones. they are chemicals released by neurons into extracellular space that then travel into the blood in search of receptor-bearing target cells
Except for gap junction signalling, Cell-to-cell signalling requires
1) Signal (Ligand)
2) Receptor
3) Way to transduce the message
What does signal transduction pathway refer too
Converts one form of signal to another to another
All cells have _____ pathways
some
Why are pathways important
Can amplify the signals
Define intracellular receptors
Are ligands usually lipophilic (Hydrophobic)
Able to diffuse through cell membranes and bind to receptors in the nucleus or cytosol
Often alter gene expression, slow but long- lasting
Ex; Cortisol, steroids
Define Cell Membrane (EXTRACELLULAR) receptors
embedded in plasma membrane
ligands are lipophobic (hydrophilic)
bind to extracellular domains of receptors causing an activation of an intracellular signal transduction pathway
Ex; Epinephrine
Intracellular signal receptors typically work with what
gene expression
What are the four main Cell membrane receptors?
1) Integrin Receptors
2) G-Protein-coupled Receptors
3) Receptor-enzyme (catalytic receptor)
4) Integrin receptor (catalytic receptor)
Define Integrin Receptors and what it is used for
Binding of the extracellular ligand leads to changes in the arrangement of the cytoskeleton or alters enzyme activity
Cell movement, growth, wound healing
Define receptor Ion channels
Receptor is a transmembrane channel
What are the 3 things receptor (ion) channels are typically called?
1) Ligand-gated ion channels
2) Neurotransmitter-gated ion channels
3) Ionotropic receptors
In Receptor ion channels, the ligand is typically a what
neurotransmitter
Binding of neurotransmitters triggers the opening of what channel
receptor ion
What channels allow Ca++ into a cell
Receptor ion channels
Ca++ is an important _________ signal
intracellular
ionotropic receptors have to do with what
the movement of ions
Define receptor enzymes
Ligands binds to receptors and an intracellular enzyme is activated amplifying the signal significantly
Describe an In depth Example of receptor enzyme: Insulin Signaling
1) INsulin is released from the pancreas when blood sugar concentration is above set-point
2) The insulin binds to tyrosine kinase receptors and induces dimerization of receptors
3) Cytoplasmic tails of the receptor will then auto phosphorylate and transfer phosphate groups from ATP to tail of receptor
4) Phosphorylated receptor tails activate a kinase located in cytoplasm which then phosphorylates other substrates needed
5) End result is the addition of GLUT transported into plasma membrane which returns concentration to normal
G-Protein coupled Receptors (GPCRs) are
ligand binds to receptor and an intracellular enzyme is activated, could also trigger opening of ion channel
All GPCRs work to produce what
secondary messengers inside the cell
What are 3 important classic secondary messengers
cAMP
cGMP
Inositol triphosphate (IP3)
Diacuglyceride (DAG)
What are 3 novel secondary messengers
a) Calcium
b) Lipids
c) Gases
What are secondary messengers also called
metabotropic receptors
GPCR consist of ___ transmembrane domains and ____ subunits
7; 3
When G-protein is active it is bound to _____
GTP
When G-protein is inactive its bound to ____
GDP
Describe the steps of GPCR Adenylyl Cyclase Signal Transduction and Amplification
1) Signal molecule binds to GPCR, which activates G protein
2) G protein turns on adenylyl cyclase (amplifier enzyme)
3) Adenylyl cyclase converts ATP to cyclic AMP (cAMP)
4) cAMP activates protein kinase A
5) Kinase A phosphorylates other proteins leading to a cellular response
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ABBREVIATIONS: What does the following stand for: PL-C DAG PK-C IP3 ER
PL-C = phospholipase C DAG = Diacylglyerol PK-C = Protein Kinase C IP3 = Inositol Trisphosphate ER = Endoplasmic Reticulum
Describe the steps in GPCR - Phospholipas3e C signal Transduction
1) Signal molecule binds to GPCR which activates a G protein
2) G protein activates phospholipase C (PL-C) which is an amplifier enzyme
3) PLC converts membrane phospholipids into DAG which remains in the membrane and IP3 which diffuses into the cytoplasm
4) DAG activates PKC, which phosphorylates proteins
5) IP3 causes releases of Ca2+ from organelles, creating a CA2+ signal
what 4 things do calcium binds to and what results from this
1) Binds to calmodulin = activation of other proteins
2) Binds to motor proteins and allows action
3) Binds to synaptic proteins to trigger exocytosis
4) Binds to ion channels to modulate their gating
What is now being recognized as secondary messengers?
Soluble gasses
NO is synthesized by what, and has a half-life of
NO-synthase, 2-30 seconds
What does NO activate
Guanylyl cyclase, Production of cGMP leads to relaxation of smooth muscle
Describe the Arachidonic Acid Cascade
1) G-protein activates Phospholipase A2 (PLA2)
2) PLA2 degrades phospholipids into arachidonic Acid (an eicosanoid)
3) Arachidonic acid metabolites and diffuse out of the cell and act as a ligand for GPCR cell membranes and adjacent cells
What does the hormone epinephrine (Adrenaline) cause some blood vessels to constrict and others to dilate
Receptor isoforms
When Epinephrine binds a-receptors it causes blood vessels to ____ where as if it binds to b2-Receptor it causes blood vessels to ________?
Constrict; dilate
True or False; A receptor can not be promiscuous
False
Phosphorylation can cause receptors to have a _____ affinity for ligands
lower
Receptor numbers can be upregulated or downregulated by what 3 things
Development
Homeostatic challenges
Disease states
The mechanism of opioid tolerance is the result of ____ being desensitized due to continuous exposure to an _____
Receptors; Agonist
Are G-proteins anchored by cytoskeleton? Why or why mot
No because cytoskeletons only exists in the cytoplasm
What does cAMP activate
PKA
What Kinase is linked with cAMP pathway, PKA or PKC
Adenylyl cyclase
Define Afferent in regards to Control pathways
back to the source
What are the two kinds of feedback loops?
Negative and Positive
Define the 3 key things that negative feedback does
1) Keeps system near a set point
2) Response acts to negate the stimulus
3) Response can Restore homeostasis, but cannot prevent the initial perturbation
Define the 3 key things that positive feedback does
1) Brings a system further from a set point
2) Response acts to reinforce the stimulus
3) Requires an outside factor to shut off
Give an example of both positive and negative feedback
Negative feedback = cruise control
Positive feedback = giving birth
Why is arachidonic acid involved in both intracellular and intercellular pathways.
It can diffuse out of the cell and have a paracrine affect on neighboring cells but can also produce an autocrine response due to being a secondary messenger
What is feedforward control?
When a small stimulus sets off a chain of events aimed at preventing a perturbation
Is positive feedback non homeostatic
no, it is
