Unit 4: Cell Communication and Cell Cycle

Homeostasis

Steady state or internal balance

When do cells maintain homeostasis?

Maintain a relatively constant internal environment even when the external environment changes significantly

Set point

Internal conditions typical state

Stimulus

Fluctuations in that condition above or below the set point serve

Sensor

A receptor or sensor detects the stimulus and triggers a response

Response

Activity that returns the condition to the set point

Negative Feedback

Response reduces the stimulus

Example of negative feedback

When you exercise, you produce heat, which increases your body temperature.

Your nervous system detects this increases and triggers sweating. As your sweat evaporates, your skin cools, returning your body to its set point.

Positive Feedback

Stimulus is amplified in order to complete a process; then the condition returns to the set point

Example of positive feedback

During childbirth, the pressure of the baby’s head against the uterus stimulates contractions.

The contractions result in greater pressure, thereby stimulating more contractions and then more pressure. This continues until the baby is born.

Methods Used by Cells to Communicate

Autocrine, Juxtacrine, Paracrine, Endocrine

Autocrine signaling

A cell sends a signal to itself

Juxtacrine signaling

Cells communicate with adjacent cells through direct contact

Two examples of juxtacrine signalling

• Ex. plasmodesmata connect plant cells and gap junctions connect animal cells

• Ex. glycoproteins on one cell interact with glycoproteins on another cell

Paracrine signalling

Cells communicate to nearby cells by releasing chemical messengers

Paracrine signalling example

Ex. neurotransmitters released into a synapse

Endocrine signalling

Cells communicate to cells far away by releasing chemical messengers that are carried to the target cell

Endocrine signalling example

Adrenaline is produced by adrenal glands, released into the bloodstream, and carried to the heart and other muscles

In all forms of cell signaling, a signal is converted to a cellular response in three steps:

1. Reception

2. Transduction

3. Response

Reception

Signaling molecule binds to the receptor protein

Transduction

The signal is converted into a form that can produce a cellular response

Response

The transduced signal triggers a cellular response

Reception process

A signal molecule, a ligand, binds to a receptor protein in a lock and key fashion, causing the receptor to change shape.

Where are receptor proteins found?

Most receptor proteins are in the cell membrane but some are inside the cell.

Locations of hydrophilic and hydrophobic ligands

1. Hydrophilic ligands bind to plasma membrane receptors

2. Small or hydrophobic ligands can pass through the membrane and attach to intracellular receptors (ex. steroid hormones like testosterone)

The three most common types of membrane receptor proteins:

• G-protein coupled receptors

• Receptor tyrosine kinases

• Ion channel receptors

The binding of ligands is how specific?

Highly specific (must be the right shape).

G-Protein Coupled Receptors

G proteins bind the energy-rich GTP (very similar to ATP- source of energy)

Do G-proteins vary in structure?

Are all very similar in structure

GPCR systems

Extremely widespread and diverse in their functions

Receptor Tyrosine Kinases (RTKs)

Membrane receptors that transfer phosphate groups from ATP to another protein

How effective are RTKs?

Can trigger multiple signal transduction pathways at once

Ion Channel Receptors

Act as a gates that open and close when the receptor changes shape

What happens when a signal molecule (like a neurotransmitter in a synapse) binds as a ligand to the receptor?

The ate allows specific ions, such as Na⁺ or Ca²⁺, through a channel in the receptor

Transduction

Molecular interactions relay signals from receptors to target molecules in the cell

How does transduction have multistep pathways?

Can amplify a signal (by activating multiple copies of the next component in the pathway)

What is the benefit of having multistep pathways?

Provide more opportunities for coordination and regulation

Multistep pathways

At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.

Transduction - Phosphorylation

1. In this process, a series of protein kinases add a phosphate to the next one in line, activating it

2. Phosphatase enzymes then remove the phosphates

Kinases

Enzymes (proteins) that add phosphate groups (PO₄³⁻) to other molecules (proteins) to change their shape and activate or inactivate them

Secondary messengers

Small molecules/ions that relay signals received by receptors to proteins.

Common secondary messengers -

• cAMP (cyclic AMP)

• Calcium

Calcium as a secondary messenger

Can function as a second messenger because its concentration in the cytosol is normally much lower than the concentration outside the cell; thus a small change in the number of calcium ions represents a relatively large percentage change in calcium concentration

Scaffolding proteins

Can increase the signal transduction efficiency.

There can be many possible responses to a cell signal -

• The same signal molecule can trigger different responses

• Many response can come from one signal

• The signal can also trigger an activator or inhibitor

• The signal can also trigger multiple receptors and different responses

Example of responses

Turn transcription of DNA on/off or regulate activity of proteins in cytoplasm.

Stopping the Response

The signal response is terminated quickly when the ligand detaches from the receptor

Mitosis

Genetic material is divided as one cell divides, forming two identical cells

What is divided during cytokinesis?

Organelles and cytoplasm

Cell cycle in unicellular organisms

Used for reproduction

• Called binary fission

Cell cycle in multicellular organisms

Used for growth and repair

Organelles Involved in the Cell Cycle

• Nucleus

  • Protects the DNA

• Cytoskeleton

  • Organizes structures in the cell

What is inlcuded in the cytoskeletan?

Centrioles

Centrioles

Responsible for the spindle fibers that guide the chromosomes during mitosis

Overview of the Cell Cycle

:)

Cells spend 90% of their time in?

Interphase

G1

• 1st Gap

  • Everyday tasks such as making proteins

  • Cell grows

G0

Cell continues doing its job until it receives a signal to reenter G1 to get ready to divide

If the cell receives a signal to divide, it moves on to the next phases:

S and G2

S

• DNA Synthesis

  • Copies genetics material (so each cell gets a copy)

G2

• 2nd Gap

  • Prepares for division

  • Cell grows more

  • Produces proteins, organelles, and membranes

What is this?

DNA in the form of chromatin (stringy)

The DNA is divided between two daughter nuclei in four phases - 

1. Prophase

2. Metaphase

3. Anaphase

4. Telophase

Prophase

• Chromatin condenses into chromosomes

• Centrioles (in animal cell) move to opposite ends of the cell

• Protein fibers form across the cell

• The nucleolus disappears

• The nuclear membrane breaks down

Metaphase

• Chromosomes line up in the middle of the cell

• Spindle fibers (attached to kinetochores) coordinate movement

Kinetochores

Complex of proteins associated with the centromere of a chromosome during cell division, to which the microtubules of the spindle attach.

Anaphase

Sister chromatids separate at kinetochores

Poles move farther apart

How are sister chromatids seperated?

• Proteins holding the sister chromatids together are inactivated

• Pulled by motor proteins “walking” along microtubules

Telophase

• Chromosomes arrive at opposite poles

• Daughter nuclei form

• Chromosomes disperse

• Spindle fibers disperse

• Cytokinesis begins

Cytokinesis for animal cells

Microfilaments contract, forming a cleavage furrow

Cytokinesis for plant cells

• Cell plate forms

• Vesicles from the Golgi fuse to form two cell membranes

• New cell wall laid down between the cell membranes

Cell Cycle Checkpoints

Serve as control points where stop and go-ahead signals can regulate the cell cycle (controlled by signals inside and outside the cell).

G2 Checkpoint: Pass or fail?

Did the DNA copy correctly in the S phase?

Pass- Cell goes to mitosis

Fail - apoptosis

M Checkpoint- Pass or fail?

When the DNA lines up in the middle (metaphase), will each cell get the same amount of DNA?

Pass- cell divides

Fail - Apoptosis

G1 checkpoint- Pass or fail?

-Do I need a new cell?

-Is this cell healthy?

-Are there enough nutrients to divide?

Pass - Cell enters S phase

Fail - Goes to G₀

“Go” signals at checkpoints results in?

Changes in molecular signals in the cytoplasm

Cyclin-dependent kinases (Cdks)

Kinases that are only active when attached to a cyclin

Cyclin

A protein that fluctuates in concentration in the cell

Cyclins and Cyclin-Dependent Kinases: What fluctuates and what doesn’t?

• The concentration on Cdks does not fluctuate. 

• The concentration of cyclins does.

How are cyclins regulated?

Certain cyclins are made at certain times during the cell cycle, and their concentration will rise and fall.  Cyclins are also destroyed after they are no longer needed by the cell. 

What is the purpose of Cdkns activity?

Initiate the next step of the cell cycle

Cdks are only active when?

Attached to a cyclin.

Growth factors

Released by some cells and stimulate surrounding cells to divide

Examples of growth factors

Ex. Platelets release platelet-derived growth factor (PDGF). Fibroblasts (connective tissue) have receptors for PDGF. When PDGF binds to the receptors, a signal transduction pathway stimulates fibroblast division. 

Density-dependent inhibition

Crowded cells stop dividing

Anchorage dependence

To divide, cell must be attached to something

Cancer cells bypass cell cycle controls by?

• May make their own growth factor

• May have an abnormal cell cycle control system

• May convey a growth factor’s signal without the presence of the growth factor

How can your immune system react to cancer cells?

The immune system normally recognizes a cells conversion from a normal cell to a cancer cell and destroys it. If it is not destroyed, a tumor can form. 

Benign

Stays in the same place

Malignant

Spreades to other parts in the body (metastaizes) 

Proto-oncogens normal function

When activated, they signal for cell division to start (G1 checkpoint)

Proto-oncogens muatetd function

The gene is always activated, so it continues to divide (ignores the G1 checkpoint)

Once mutated, a proto-oncogene is called an?

Onocogene

Is the mutation for a proto-oncogen is dominant or recessive?

Dominant - only one copy of the defective gene is needed to impact the cell

Tumor Suppressor Genes normal function

Slow cell division, repair mistakes, or apoptosis

Tumor Suppressor Genes mutated function

Cell does not stop division if mistakes are found

Is the mutation for tumor supressor genese dominant or recessive?

Recessive - both copies of the gene must be mutated to impact the cell

Chemotherapy

Drugs disrupt any cells going through mitosis; used in wide spread cancers

Radiation

High energy beams (mostly X rays) are emitted onto a cancerous body part, causing mutations in the DNA to the point where the cell cannot divide

Immunotherapy

Trains the immune system to recognize cancerous cells and kill them off