How do cells in direct contact communicate?
Gap junctions
How do cells not in direct contact communicate?
Autocrine, paracrine, endocrine secretions, and neurotransmitters
What are gap junctions made of?
Connexons
Which types of molecules can pass through gap junctions?
Ions and signalling molecules
Excitable cells
Why do cardiac muscle cells pass signals through gap junctions?
To coordinate heart contraction
Why do gap juctions open and close?
To defend against possible danger from a neighbouring cell
Autocrine, paracrine, endocrine secretions, and neurotransmitters are a type of...?
Extracellular communication
What are autocrine secretions?
Substances released by a cell that affect the same cell
What are paracrine secretions?
Substances released that affect nearby cells
What are endocrine secretions?
Substances released that affect distant cells
What are neurotransmitter secretions?
Substances released by a nerve terminal into the synapse
What do endocrine secretions diffuse through?
The bloodstream
Where do synaptic secretions occur?
Where a nerve cell axon terminates on a target cell
What must secretions interact with to have a effect on a target cell?
A receptor
What are neurotransmitters released by during neurotransmission?
The presynaptic neuron
What are the components of signal transduction?
The signal, the receptors, the signalling proteins, and the second messengers
The signal of signal transduction can be..? (select all that apply)
Membrane permeable
Membrane impermeable
Membrane-permeable signal molecules bind to receptor proteins found where?
In the cytosol
What do membrane-impermeable signal molecules bind to?
Transmembrane cell surface receptor proteins
What do transmembrane cell surface receptor proteins activate?
The second messengers
Nuclear effectors are also called..?
Transcription factors
What are the pathways of signal transduction?
Linear, convergent, divergent, multi-branched
What are signals also called?
Ligands
What is a ligand?
A substance that forms a complex with a biomolecule for a biological purpose
Which receptor controls your ability to detect smell and the fight or flight response?
G-Protein coupled receptors
What does a ligand bind to?
A site on a target protein
Are steroids membrane permeable or impermeable?
Membrane permeable
Membrane-permeable signal molecules/ligands can penetrate the membrane AND interact with cytosolic receptors. True or False?
True
What are the physical signals? (select all that apply)
Light
Pressure
Temperature
What is the range of the GPCR transmembrane domains?
H1 --> H7
What are the subunits of the heterotrimeric G-protein?
Alpha, beta, and gamma
What happens when a ligand binds to a GPCR?
A conformational change in shape and the activation of the coupled G-protein subunits
Which receptor transmits signal information allowing ions to flow from one side of the membrane to another?
Ion channel receptors
The pores of the ion channel receptors open so ions can flow through when what happens?
When its ligand binds causing a conformational change
Are ion channel receptor proteins enzymes?
No
Which receptor controls voluntary muscle contraction?
Ion channels
Acetylcholine is a ____ and its release fosters communication between nerve cells?
neurotransmitter
Where is the receptor gunaylate cyclase found?
Bound to the membrane and soluble in the cytosol
What are the domains of membrane-bound guanylate cyclase? (select all that apply)
Externalized ligand binding domain
Transmembrane domain
Internal catalytic domain
What role do guanylate cyclases play in vision?
They convert light signals into electrical signals in the eye
WHEN THE RECEPTOR IS ACTIVATED...what does the catalytic domain of membrane-bound cyclase do?
Converts GTP to cGMP (cyclic guanosine monophosphate)
What is the function of protein kinases?
To phosphorylate proteins containing serine, threonine, and tyrosine residues
In a clinical setting: The dysfunction of protein kinases is associated with the development of ____?
cancers
What are the 2 types of protein kinases receptors?
RTK
S/TKR
What does RTK phosphorylate?
Tyrosine
What does S/TKR phosphorylate?
serine and threonine
What are the steps of the binding of a ligand to RTK? (in order)
Inactive --> Dimerization --> Transautophosphorylation --> Binding sites --> Resetting
Fill in the blanks for the inactive stage of a ligand binding to RTK: "Before ligand binding inactive receptors are separate ____ with inactive _____ domains."
polypeptides, tyrosine kinase
Binding to a signalling molecule causes the 2 subunits of the tyrosine kinase receptor to dimerize forming what?
A dimer
What is is called when the cytoplasmic tail of a subunit comes close to the tyrosine kinase domain of another causing the opposite domain to be phosphorylated on a tyrosine amino acids?
Transautophosphorylation
After transautophosphorylation the phosphotyrosine amino acids become what for signalling proteins?
Binding sites
When a ligand binds to RTK what dephosphorylates the amino acids in the final stage (resetting)?
phosphoprotein phosphatases
What are the functions of transmembrane scaffolds? (select all that apply)
brings signalling proteins together & regulates signal transduction
localizes signalling proteins to cellular areas & isolates signalling pathways
Where are nuclear receptors found?
In the cytosol
What do nuclear receptors bind to inside the nucleus to control the expression of genes?
Steroid response elements (SREs)
What are nuclear receptors also called?
Transcription factors
Which receptor plays a role in yur response to toxic substances (ie. tobacco)
Nuclear recptors
What are the 2 features of all signalling proteins?
Mobility and catalysis
What is the function of signalling proteins?
To transmit and amplify signalling information
What mobilizes second messengers?
Signalling proteins
What are the 2 classes of G-proteins? (select all that apply)
Heterotrimeric G-proteins
True or False: Monomeric G-proteins are not coupled to GPCRs.
True
True or False: Monomeric G-proteins are single polypeptides with 2 binding sites and a GTPase domain.
True
How many polypeptides do heterotrimeric G-proteins have?
3
Concerning heterotrimeric G-proteins, which subunit is analgous monomeric G-protein (by binding to GTP/GDP & a target protein)?
The alpha subunit
What is the primary function of the beta/gamma subunits in regards to heterotrimeric G-proteins?
To stabilize the inactive alpha subunit
What are the 4 steps in the activation of G-proteins?
1. binding 2. separation 3. propagate 4. cleave & reform
Activation of G-proteins, step 1. binding: The heterotrimer with alpha & beta/gamma subunits is bound to what?
GDP
Activation of G-proteins, step 2. separation: before separation, GDP is exchanged with GTP where?
On the alpha subunit
Which of these is an effector?
Adenylate cyclase
Activation of G-proteins, step 4. cleave & reform: Which subunit(s) binds to reform the heterotrimer?
beta/gamma
True or False: The majority of protein kinases are non-receptor cytosolic signalling proteins.
True
True or False: Protein kinases that enter the nucleus can interact with DNA.
False
Is Ca2+ kept at low or high intracellular concentrations?
Low
When Ca2+ concentrations increase by a signalling effect, it interacts with proteins causing a ____ effect.
downstream
Which of these is a Ca2+ binding protein?
Calmodulin
True or False: Adenylyl cyclase is a signalling protein.
True
What are the 2 types of heterotrimeric G-protein alpha subunits?
αₛ and αᵢ
Why is adenylyl cyclase a signalling protein and not a receptor?
It binds to the alpha subunit of heterotrimeric G-proteins
Lipid kinases are signalling proteins. What do they do?
Phosphorylate phospholipids
Lipid kinases will add a phosphate to which part of a phospholipid?
The polar head group
What does phosphorylation of the polar head group do for a phospholipid?
Changes its shape and allows it to bind to its target protein
What is an adapter protein? (select all that apply)
A signalling protein
Protein domains that allow parts of the signalling cascade to be spatially close
Ligands are the....?
First messengers
What are second messengers?
Non-protein ions/molecules formed/released during signal transduction
True or False: Second messengers are small, diffuse rapidly, and stay in the cytosol for long periods of time.
False
Which enzyme degrades the second messengers cAMP and cGMP?
Phosphodiesterases
Which of these second messengers are sequestered into cellular organelles?
Ca2+
Why is signal amplification important in the cell?
It allows a small signal to produce a substantial effect in the cell
Hormones and growth factors are....?
Soluble signals
Second messengers include....? (select all that apply)
Ions
Nucleotides
Lipids and hydrocarbons
Extracellular matrix molecules and nearby cells are....?
Insoluble signals
What are the steps of the heterotrimeric signalling cascade in order?
1. GPCRs 2. cAMP 3. PKA 4. CREB
What happens after CREB binds with CBP?
They interact with DNA to start transcription
What are the steps of the phospholipid kinase signalling cascade in order?
1. GPCR 2. PLC 3. PIP2/IP3 4. Ca2+ 5. PKC
What are the steps of the protein kinase signalling cascade in order?
1. FGFs 2. Grb2 3. Erk
Which of these is homodimeric?
FGFR
In the kinase signalling cascade: what binds to and activates Ras?
Sos
In the kinase signalling cascade: what binds to phosphotyrosine, changes shape, then binds to Sos?
Grb2
In the kinase signalling cascade: what binds to FGFRs?
FGF
In the kinase signalling cascade: what undergoes transautophosphorylation to form phosphotyrosines?
FGFR
In the kinase signalling cascade: what forms a dimer that phsophorylaytes proteins in the cytosol or nucelus?
Erk
What are lysosomes?
Organelles that break down misfolded and damaged organelles, nucleic acids, and lipids
What are proteasomes?
Protein complexes that break down damaged and misfolded proteins in the nucleus and cytosol
What are peroxisomes?
Small membrane bound organelles that acts as a site of degradation for reactions that produce reactive oxygen species (ROS). Contains the enzyme catalase to neutralize these reactions
How is cargo delivered to the lysosome?
By an endosome
What tag is used to send cargo to the lysosome?
M6P
What are vesicles digested by?
Proteases
Select all that are carried by vesicles.
Membrane proteins
Soluble proteins
Proteases
Where are proteases made?
In the endoplasmic reticulum
Do lysosomes break down endogenous or non-endogenous proteins?
Non-endogenous
Where are molecules sent after being broken down by the lysosomes?
The cytosol
What does the glycocalyx do?
Prevents lysosomes from digesting themselves
Do proteasomes degrade endogenous or non-endogenous proteins?
Endogenous
Which organelle requires ubiquitination?
Proteasomes
What are damaged or misfolded cytosolic proteins tagged with?
A polyubiquitin chain
What is ubiquitin?
A regulatory protein attached to another protein which labels them for destruction by a proteasome
Can proteasomes be found in the nucleus?
Yes
Why are proteasomes also found in the nucleus?
So the cell can degrade unwanted nuclear proteins without exporting them to the cytosol
What are peroxins?
Essential peroxisome proteins
How are peroxins targeted to the peroxisome?
Peroxisomal targeting signals
Enzyme used by peroxisomes to keep the cell safe from ROS?
Catalase
What is apoptosis?
Programmed cell death triggred by normal, healthy processes in the body
Other than protecting the body from damaged cells, what function does apoptosis serve?
Development - removing webbing between fingers and toes in fetuses
Order the 4 steps of the mechanism of apoptosis.
1. Initiation 2. Membrane blebbling & enzyme activation 3. Cell structure changes 4. Engulfment
Mechanism of apoptosis: Which 2 pathways initiate apoptosis?
Intrinsic and extrinsic
Where does the intrinsic pathway originate?
The outer membrane of the mitochondria
Which signals will trigger the intrinsic pathway? (select all that apply)
Intracellular signals
Which signals trigger apoptosis?
External signals
Which receptor does the the extrinsic pathway use?
Death receptor
In apoptosis, neighboring cells will release what to bind to death receptors on the damaged cell?
Death ligands
In apoptosis, which enzyme is activated during membrane blebbing & enzyme activation?
Caspases
In apoptosis membrane blebbing & enzyme activation, initiator caspases activate which other caspases?
Executioner caspases
In apoptosis, what happens to DNA after executioner caspases are activated?
DNA is fragmented between histones & DNA repair stops
True or False: The nuclear membrane breaks down and the nucleus disappears during apoptosis.
True
In apoptosis, what is exposed on the exoplasmic leaflet after the cytoskeleton disassembles?
PS (phosphotidyl serine)
In apoptosis, what endocytoses the apoptic bodies for disposal?
Phagocytes
Order the 3 steps of the mechanism of necrosis.
1. Damage 2. Swelling 3. Destruction
In necrosis, what forms in the cells during swelling?
Vacuoles
What is ischemia?
When blood flow is stopped to tissues
What is necrosis?
Premature cell death following injury
In necrosis, the cellular content spills out producing what?
Inflammatory signals
In necrosis, nearby cells are exposed to the mitochondrial proteins, degraded DNA, and lysosomes. What then happens to these nearby cells?
Damaged or have apoptosis triggered