AP Biology Unit 4: Cell Communication and Signal Transduction

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Cell Communication and Signal Transduction

• cell to cell communication is critical for the function and survival of cells

• responsible for the growth and development of multicellular organisms

  How do cells communicate?

  1. Direct contact

  2. Local signaling (paracrine)

  3. Long-distance signaling (endocrine)

Direct Contact:

• communication through cell junctions

• signaling substances and other material dissolved in the cytoplasm can pass freely between adjacent cells

  • animals cells: gap junctions

  • plant cells: plasmodesmata

  example: immune cells a antigen-presenting cells (APCs) communicate to T cells through direct contact (inducing an immune response)

Local Signaling ( Regulators ):

• local regulators: a secreting cell will release chemical messages (local regulators/ligands) that travel a short distance through the extracellular fluid

• the chemical messages will cause a response in a target cell

  example: autocrine signaling, paracrine signaling, synaptic signaling

• cells can also signal themselves autocrine signaling

• paracrine signaling: secretory cells release local regulators via exocytosis to an adjacent cell ex: growth factors, synaptic signaling

• Synaptic signaling: occurs in animal nervous systems

neurons secrete neurotransmitters. diffuse across the synaptic cleft space between the nerve cell and target cell

Long-distance signaling:

• animals and plants use hormones for long-distance signaling

  • plants release hormones that travel in the plant vascular tissue (xylem and phloem) or through the air to reach target tissues

  • Animals use endocrine signaling

    • specialized cells release hormones into the circulatory system where they reach target cells

      example: insulin: released by the pancreas into the bloodstream where it circulates through the body and binds to target cells

Cell Signaling

three stages

1. reception: ligand binds to the receptor

2. transduction: signal is converted

3. response: a cell process is altered

stage 1: Reception

reception: (getting the signal) the detection and receiving of a ligand by a receptor in the target cell

• receptor: macromolecule that binds to a signal molecule (ligand)

  • all receptors have an area that interacts with the ligand and an area that transmits a signal to another protein

    • binding between ligand and receptor is highly specific

• when the ligand binds to the receptor, the receptor activates (via a conformational change)

• allows the receptor to interact with other cellular molecules

  • initiates transduction signal

• receptors can be in the plasma membrane or intracellular

stage 2: Transduction

transduction: the conversion of an extracellular signal to an intracellular signal that will bring about a cellular response

• requires a sequence of changes in a series of molecules known as a signal transduction pathway

• the signal transduction pathway regulates protein activity through:

  • phosphorylation by the enzyme protein kinase

    • relays signal inside the cell

  • dephosphorylation by the enzyme protein phosphatase

    • shuts off pathways

    remember: a change in shape means a change in function

Signal transduction pathways

• a series of steps where a signal on the cell surface is converted into a cellular response

• can influence how a cell responds to its environment

• can result in changes in gene expression and cell function

  • can alter phenotypes or result in cell death

• mutations to receptor proteins or to any component of the signaling pathway will result in a change to the transduction of the signal

• transduction-advantages of lots of steps

  • amplification: a few molecules can produce a large cellular response

  • more opportunities for coordination and regulation of the cellular response

Protein Phosphorylation

• many pathways involve a cascade of protein phosphorylations to transmit a signal

• protein kinases transfer phosphates from ATP to a protein (phosphorylation)

• protein phosphatases remove the phosphates from proteins (dephosphorylation)

Stage 2: Transduction continued

• During transduction the signal is amplified

• second messengers: small, non-protein molecules and ions help relay the message and amplify the response ex: cyclic AMP (cAMP) and ca+ ions.

Cyclic AMP

• one of the most widely used second messengers

• Adenylyl cyclase: an enzyme in the cell membrane that converts ATP to cAMP in response to a signal

• cAMP usually activates a phosphorylation cascade

Stage 3: Response

Response: the final molecule in the signaling pathway converts the signal to a response that will alter a cellular process.

• ex: a protein that can alter membrane permeability, an enzyme that will change a metabolic process, a protein that turns genes on or off

Important Receptors

• in eukaryotic organisms, there are 3 main categories of cell membrane receptors

  • G protein-coupled receptors (GPCR’s)

  • Receptor Tyrosine Kinases (RTKs)

  • Ion channels

GPCRs

G protein-coupled receptors (GPCRs):

• the largest category of cell surface receptors

• important in animal sensory systems

• binds to a G protein that can bind to GTP, which is an energy molecule similar to ATP

• The GPCR, enzyme, and G protein are inactive until ligand binding to GPCR on the extracellular side (on-off switch)

• ligand binding causes the cytoplasmic side to change shape

  • allows for the G protein to bind to GPCR

  • activates the GPCR and G protein

  • GDP becomes GTP

• part of the activated G protein can then bind to the enzyme

  • activates enzyme

  • amplifies the signal and leads to a cellular response

• G protein-coupled receptors work with a G protein

  • G protein acts as an on-off switch

  • if GDP is attached, a G protein is inactive

  • if GTP is attached, G protein is active

Receptor Tyrosine Kinases

• attaches phosphates to tyrosines and can trigger multiple transduction pathways at once.

Ion Channels

Ligand-gated ion channels:

• located in the plasma membrane

• important in the nervous system

• receptors that act as a “gate” for ions

  • when a ligand binds to the receptor, the “gate” opens or closes allowing the diffusion of specific ions

  • initiates a series of events that lead to a cellular response

• ex: calcium-gated ion channels

Calcium Ions

• calcium ions (Ca+2) are important second messengers because cells can regulate their concentration

Intracellular Receptors

• when nonpolar or really small chemical messengers cross the membrane, they bind to receptors inside the cell (intracellular = “inside cell”)

• ex: steroids

• activated hormone receptor complexes in the cell can act as transcription factors

Homeostasis and Feedback

• Set Point: values for various physiological conditions that the body tries to maintain

  • this set point has a normal range for which it can fluctuate

  • ex: body temp (set point = 98.6 F Normal range 97 F - 99 F)

• Homeostasis: The state of relatively stable internal conditions

  • organisms detect and respond to a stimulus

  • think: Balance

  • the body maintains homeostasis through feedback loops.

Feedback Loops

• two types of feedback loops: negative and positive

• terms to know:

• Stimulus: a variable that will cause a response

• Receptor/Sensor: sensory organs that detect a stimulus. this information is sent to the control center (brain)

• Effector: muscle or gland that will respond

• Response: changes (decreases or increases) the effect of the stimulus

Negative Feedback

• the most common feedback mechanism

• this type of feedback reduces the effect of the stimulus

  • ex: sweat, blood sugar, breathing rate

Positive Feedback

• this type of feedback increases the effect of a stimulus

  • ex: child labor, blood clotting, fruit ripening

Homeostatic Imbalances

• reasons why the body may not be able to regulate homeostasis

  • ex: genetic disorders, drug or alcohol abuse, intolerable conditions (extreme heat or cold)

• Disease: when the body is unable to maintain homeostasis

  • ex: cancer (the body cannot regulate cell growth) & diabetes (the body cannot regulate blood glucose levels)

Cell signaling as a means of Homeostasis

• in order to maintain homeostasis, the cells in a multicellular organism must be able to communicate

• communication occurs through signal transduction pathways

Cell Cycle

Cell Cycle

• the cell division process is an integral part of life

  • allows for the reproduction of cells, growth of cells, and tissue repair

• cell cycle: the life of a cell from its formation until it divides

Organization of DNA

• cells must organize and package their DNA before division

• DNA associates with and wraps around proteins known as histones to form nucleosomes

  • strings of nucleosomes form chromatin

    ◼︎ when a cell is not actively dividing, chromatin is in a non-condensed form

    ◼︎ after DNA replication, chromatin condenses to form a chromesome

    ◼︎ chromosomes are densely packed to allow for easier divisioni

• since the DNA was replicated, each chromosome has a duplicated copy

• these copies join together to form sister chromatids

  • centromere: the region on each sister chromatid where they are most closely attached

  • kinetochore: proteins attached to centromere that link each sister chromatid to the mitotic spindle

Genome

• Genome: all of a cell’s genetic information (DNA)

• Prokaryotes: singular, circular DNA

• Eukaryotes: one of more linear chromosomes

  • every eukaryote has a specific number of chromosomes

    ◼︎ Humans: 46

    ◼︎ Chimps: 48

    ◼︎ Elephants: 56

• Homologous chromosomes: two chromosomes (one from mom and one from dad) that are the same length, have the same centromere position, and carry genes controlling the same characteristics

Types of Cells

Cell Cycle

• the cell cycle consists of alternating phases of interphase and mitosis

  • G1 → S → G2 → mitosis → cytokinesis

    ↪︎Interphase↩︎

Interphase

• the longest portion of the cell cycle (90%)

  • G1 “first gap” phase

    ◼︎ the cell grows and carries out normal functions

  • S “synthesis” phase

    ◼ DNA replication and chromosome duplication occurs

  • G2 “second gap” phase

    ◼ final growth and preparation for mitosis

M phase

• Mitosis: nucleus divides

• Cytokinesis: cytoplasm divides

• mitosis results in 2 indentical diploid daughter cells

• broken down into 5 stages

  1. prophase

  2. prometaphase

  3. metaphase

  4. anaphase

  5. telophase and cytokinesis

  1. Prophase

  • chromatin condenses

  • nucleoli disappear

  • duplicated chromosomes appear as sister chromatids

  • mitotic spindle begins to form

  • centrosomes move away from each other

  2. Prometaphase

  • nuclear envelope fragments

  • microtubules enter nuclear area and some attach to kinetochores

  3. Metaphase

  • centrosomes are at opposite poles

  • chromosomes line up at the metaphase plate

  • microtublues are attached to each kinetochore

  4. Anaphase

  • sister chromatids seperate and move to opposite ends of the cell due to the microtubules shortening

  • cell elongates

  5. Telophase

  • two daughter nuclei form

  • nucleoli reappear

  • chromosomes become less condensed

  5. Cytokinesis

  • Animal: a cleavage furrow appears due to a contractile ring of actin filaments

  • plants: vesicles produced by the golgi travel to the middle of the cell and form a cell plate

Binary Fission

• mitosis in eukaryotes likely evolved from binary fission in bacteria

  • single circular chromosome

  • no membrane-bound organelles

• a possible progression of mechanisms intermediate between binary fission and mitosis seen in modern organisms

Regulation of the Cell Cycle

• throughout the cell cycle there are checkpoints

  • control points that regulate the cell cycle

    ◼ cells recieve stop/go signals

Major Checkpoints

G1 Checkpoint

• most important checkpoint

• checks for cell size, growth factors, and DNA damage

• “Go” - cell completes the whole cell cycle

• “Stop” - cell enters a nondividing (quiescent) state known as G0 ( G zero) phase

G0

• non dividing stage

• some cells stay in G0 forever (muscle/nerve cells)

• some cells can be called back into the cell cycle (liver cells)

G2 Checkpoint

• checks for completion of DNA replication and DNA damage

• “Go” - cell proceeds to mitosis

• “Stop” - cell cycle steps and the cell will attempt to repair damage

  • if damage cannot be repaired the cell will undergo apoptosis

    ◼ programmed cell death

M (Spindle) Checkpoint

• checks for microtubule attachment to chromosomes at the kinetochores at metaphase

• “Go” - cell proceeds to anaphase and completes mitosis

• “Stop” - cell will pause mitosis to allow for spindles to finish attaching to chromosomes

  

Internal Cell Cycle Regulators

• cell cycle inernal control system:

  1. Cyclins (proteins)

     • concentration of cyclins varies

       ◼ cyclins are synthesized and degraded at specific stages of the cell cycle

  2. Cyclin-dependent kinases (CDK's) [enzymes]

     • concentration remains constant throught each phase of the cell cycle

       ◼ active only when its specific cyclin is present

     • phosphorylates cellular proteins

• each cyclin-CDK complex has a specific regulatory effect

  • active CDK complexes phosphorylate target proteins, which help regulate key events in the cell cycle

External Cell Cycle Regulators

• Growth factors: hormones released by cells that stimulate cell growth

  • signal transduction pathway is initiated

    ◼ CDKs are activated leading to progression through the cell cycle

• Contact (or density) inhibition: cell surface receptors recognize contact with other cells

  • initiates signal transduction pathway that stops the cell cycle in G1 phase

• Anchorage dependence: cells rely on attachment to other cells or the extracellular matrix to divide

Cancer

• Evasion of the Cell Cycle

• normal cells become cancerous throught DNA mutations (ex: in proto-oncogenes or tumor-suppressor genes)

  • DNA mutations: changes in the DNA

    ◼ cancer cells on average have accumulated 60 or more mutations on genes that regulate cell growth

Cancer Cells

• the uncontrollable growth of cancer cells can lead to a tumor

  • a mass of tissue formed by abnormal cells

    ◼ Benign tumor: cells are abnormal, but not considered to be cancerous (yet)

    • cells remain at only the tumor site and are unable to spread elsewhere in the body

    ◼ Malignant tumor: mass of cancerous cells that lose their anchorage dependency and can leave the tumor site

    • Metastasis: when cells seperate from the tumor and spread elsewhere in the body