Unit 4 Cell Communication and Cell Cycle Mega set

Cell Communication Types

1. Juxtacrine - Direct contact

2. Paracrine - Short distances

3. Endocrine - Long distances

Ligands

• biochem definition - molecule that forms a complex with another molecule to fulfill a biological function

• Molecule sending the signal

Receptor

molecule receiving the signal

Ligand-Receptor Complex

complex created when ligand and receptor combined

Juxtacrine

Signaling through direct contact between cells

• membrane bound ligand receptor complexes

• cytoplasmic connections

Only when the cell has signs of infections visible on its cell membrane

BPQ

At which stage in this virus’s life cycle would this cell be recognized as an infected cell by the immune system?

Cytoplasmic Connections

1. Gap Junctions

   • Animals

2. Plasmodesmata

   • Plants

Paracrine

Short distance communications

• neighboring cells

Development of body parts

regulated by paracrine signaling that leads to different expression of developmental genes

Synapses

Neurotrasmitters carries action potential from nerve cell to nerve cell

• through synapses, then attach to receptor on receiving cell

Endocrine

• Long distance signaling

Important Reminders

1. Receptors are selective but not perfect

   • Dopamine/Morphine

2. Not every cell will have a receptor for every ligand

3. Some cells will have different responses to the same ligand

   • Epinephrine

     • increases heart rate

     • dilates blood vessels

     • releases glucose from the liver

4 Steps of Signal Transduction

1. Signaling

   • Cell A creates a ligand

2. Reception

   • Ligand binds to receptor on Cell B

3. Transduction

   • Pathways connect Reception to Response

4. Response

   • Cell B undergoes desired change

Signal Transduction

transmission of a molecular signal from outside to inside the cell to induce a biological response

3 Methods of Reception

1. Intracellular receptors

2. Ligand gated ion channels

3. Cell surface receptors

3 Responses

1. Cellular metabolism

   • Target: cytoplasmic enzyme

2. Cell shape/movement

   • Target: cytoskeletal elements

3. Gene expression

   • Target: nuclear gene

Gene expression response target

nuclear gene

Cellular Metabolism response target

cytoplasmic enzyme

Cell shape/movement response target

cytoskeletal elements

Pathway

a series of molecular interactions in a biological system

ex. glycolysis

Cascade

a signaling pathway

Upstream - toward the signal

Downstream - toward the response

Common Patterns in Signal Transduction

1. Secondary Messengers

2. Phosphorylation

3. Signal Amplification

Secondary Messengers

Small, non-protein molecules that pass along the signal

• original ligand is the primary messenger

• ex.

  • Na+

  • Cl-

  • Ca+

  • cAMP

    • created by Adenylyl Cyclase

cAMP

created by adenylyl cyclase

secondary messenger

Phosphorylation

Many proteins are turned “On/Off” by adding a phosphate and turned “Off/On” by removing a phosphate

• phosphate typically linked to one of the three amino acids that have hydroxyl (-OH) groups in their side chains

  • tyrosine, threonine, serine

Kinase - enzyme that adds a phosphate

Phosphatase - enzyme that removes a phosphate

3 Amino Acids with Hydroxyl (can be phosphorylated)

tyrosine, threonine, serine

Signal Amplification

The signal from one ligand-receptor complex can be amplified as the signal moves downstream

Signals that amplify more are sensitive to weak targets and have a more dynamic range—have better detection

BPQ

What is the benefit of signal amplification?

Intracellular Receptors

The ligand (primary messenger) passes through the cell membrane and forms a complex with an intracellular receptor in the cytoplasm or nucleus

Lactase Expression

Lactose forms a complex with Lac 9 which activates the expression of lactase

Gene expression allows lactase to only be made when it is needed (lactose is present)

BPQ

Why is lactase activity regulated by gene expression rather than kinase activity?

Ligand Gated Ion Channels

Ligand opens an ion channel

• Ion acts as a secondary messenger

Ca+ and Muscle Contraction

Ca+ acts as a secondary messenger, connecting an electrical impulse to muscle cell contractile proteins (sarcomeres)

Cell Surface Receptors

1. G Protein coupled receptors

2. Enzyme linked receptors

G Protein

consists of 3 subunits and a guanosine phosphate (GTP or GDP)

G Protein Coupled Receptors - Transduction process

1. G Protein with GDP associates with the receptor

2. Ligand binds

3. GDP is swapped with GTP

4. G protein subunits dissociates

5. Create downstream effects

Epinephrine Transduction in the Liver

Epinephrine leads to glycogen breakdown in liver

Enzyme linked receptors

receptors form dimers with phosphorylated tyrosine that can activate multiple proteins

Transduction Process

1. Inactive receptor

2. Ligand binds

3. Forms dimer with another receptor

4. Kinase phosphorylates tyrosine on the receptors

5. Intracellular proteins bind to phosphate docking sites

This receptor’s tyrosine dock inside the cell can interact with several enzymes once activated, allowing for many different types of responses. (???)

BPQ

Enzyme linked receptors are often responsible for the regulation of cell growth, proliferation, and differentiation. What aspect of these receptors make them well designed for such complex jobs?

“OR” Gate

• Some signal transduction pathways can be activated by different receptor ligand complexes

  • Logical ____

“AND” Gate

• Some signal transduction pathways require activation from two different receptor ligand complexes

  • Logical ____

Kinase

enzyme that adds a phosphate

Phosphatase

enzyme that removes a phosphate

Homeostasis

• the tendency to resist change in order to maintain a stable, relatively constant internal environment

• Setpoint - the level at which is being maintained

Signal Regulation

Regulate signals thru

1. Metabolism

   • Break down the signal

2. Feedback

   • Negative - response to a signal decreases the signal

   • Positive - response to a signal increases the signal

Metabolism

• many hormones are broken down in liver and kidneys

  • puts time limit on hormone effectiveness

• Kidney and liver disease often lead to hormone imbalance

mRNA Metabolism

• RNA is less stable than DNA

  • mRNA is given a 5’ cap and a 3’ poly A tail to protect it

• Cytoplasm is full of de-capping proteins and exonuclease

  • Exonucleases - enzyme that removes nucleotide one at a time

  • mRNA is intentionally broken down

  • mRNA can have a half life of a few minutes

mod RNA wont make you sick but still allows your cells to make spike proteins

mod RNA also lasts longer bc its not recognized by exonucleases, so it makes more proteins bc stays in cytoplasm longer

BPQ

mRNA COVID vaccines use ModRNA or modified RNA.  These RNA have modified bases that are still recognized by ribosomes.  What is the likely reason for using this type of RNA?

Feedback loops

1. Negative Feedback Loop

   • Counters signal

   • Maintain homeostasis setpoint

2. Positive Feedback loop

   • amplify signal

   • moves away from homeostasis

   • moves toward completion (endpoint)

Insulin Negative Feedback Loop

1. Blood sugar gets high

2. Pancreas releases insulin

3. cells uptake glucose

4. blood sugar gets low

5. pancreas releases glucagon

6. liver releases glucose

Oxytocin Positive feedback loop

1. Oxytocin leads to contractions

2. contractions lead to more oxytocin

3. birth ends the cycle (endpoint)

Exonucleases

enzyme that removes nucleotide one at a time

Cell Cycle

• Interphase

  • G1

  • S Phase

  • G2

• M Phase

  • Mitosis

    • Prophase

    • Metaphase

    • Anaphase

    • Telophase

  • Cytokinesis

Checkpoints

• G1 Checkpoint

• G2 Checkpoint

• M Checkpoint

Interphase

• G1

• S Phase

• G2

• Cell Growth

• Cell spends most of its time here

  • Some exceptions: embryo

• Chromosome are uncondensed chromatin

G1

• Gap 1

  • G for “Growth”

• Cell increases in size

• Organelles are duplicated

• Proteins for S Phase are translated

S Phase

• Synthesis Phase

  • synthesize DNA

• DNA is replicated

• Centrosomes are replicated (animals)

  • Centrosome - microtubule organizing centers

Chromosomes

• Eukaryotic DNA is linear

  • linear segments are called ____

• During S Phase DNA is duplicated

• Identical DNA strands are connected by a centromere

  • 1 chromosome = 2 sister chromatids

Centrosome vs Centriole

• Centrosome - whole structure

• Centriole - complex cylinders of tubulin at the center of a centrosome

animals only

G2

• Gap 2

  • think “MORE growth”

• Prep for M Phase

• last minute DNA repair

M Phase (Mitotic phase)

• M Phase - cell division

  • Mitosis - nuclear division (PMAT)

    • Prophase

    • Metaphase

    • Anaphase

    • Telophase

  • Cytokinesis - cytoplasmic division

Prophase stages

1. Early Prophase

2. Late Prophase

Early Prophase

• Chromosomes condense

• mitotic spindles form

  • Microtubules grow between centrosomes

• Nucleolus breaks down

Late Prophase

• Chromosomes condense more

• Nuclear envelope breaks down

• Microtubules start to capture chromosomes

  • Binds on kinetochores - proteins surrounding the centromere

Kinetochore

attachment site for microtubules around the centromere

Centromere

central region of chromosome where two sister chromatids connect

Metaphase

• Every kinetochore is attached to a spindle fiber

• Chromosomes align along the metaphase plate

Anaphase

• Proteins connecting sister chromatids dissolve

  • Sister chromatids become their own chromosomes

• Chromosomes move to opposite poles

  • Microtubules attached to kinetochores shorten

  • Microtubules attach to other microtubules elongate

Telophase

• Mitotic spindle is broken down

• Nuclear envelope reforms

• Nucleolus reforms

• Chromosomes decondense

• Cytokinesis begins at same time

Cytokinesis

• Cytoplasmic division

  • NOT a part of Mitosis

• Animals - Cleavage furrow

• Plants - Cell plate

Cleavage Furrow

animals

• Cell mem pulled tgt by actin and myosin filaments

  • same proteins in muscle fibers

Cell plate

plants

• vesicles filled with cell wall components are aligned in middle

• eventually form membrane and cell wall between two cells

Checkpoints

• stages where requirements must be met for a cell to proceed thru cell cycle

• G1 CP

• G2 CP

• M CP

G1 Checkpoint

Checks

1. Size

2. Nutrients

3. DNA Integrity

4. Cell Signals (growth factors)

If Fails Check

• cell enters G₀ until it passes check

• Not necessarily bad thing

  • Most of your cells are in G₀

G2 Checkpoint

Checks for

1. DNA Synthesis

2. DNA damage

• DNA cant be repaired

  • Apoptosis - programmed cell death

Apoptosis

Programmed cell death

• deleting cells in development

• injured cells

• DNA damage

• Viral infections

Necrosis

• Unprogrammed Cell death

• Messy/harmful to surrounding cells

M Checkpoint

• AKA spindle checkpoint

Checks

• Spindle fibers are connected to all kinetochores

• makes sure Anaphase does not start too early

• otherwise chromosomes could be left behind!

Cell Cycle Regulators

1. Cyclins

2. Cyclin dependent Kinases (CdKs)

Cyclins

• 4 types that are present at different stages of the cell cycle

• Activate CdKs

Cyclin dependent Kinases (CdKs)

• Present throughout cell cycle

• need to pair with cyclin to be active

• they are Kinases!

  • turn on/off other proteins through phosphorylation

Cancer

• Loss of cell cycle regulation

General Characteristics

• Blast thru G1 CP

• Ignore Apoptosis signals

• Avoids cell cycle limitations

  • Telomerase

  • Circular chromosomes

• Promotes new blood vesicles (angiogenesis)

• Migrate to new locations (metastasis)

• Gets too big and dies (necrosis)