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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