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Unit 4: Cell Communication and Cell Cycle

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CELL COMMUNICATION + APOPTOSIS

Cells communicate with each other via chemical signals

Intro to nervous and endocrine systems

Cell-to-cell communication is essential for all organisms

E.g. flight or fight response is triggered by a signaling molecule (epinephrine)

Signal Transduction Pathway: series of steps that take place when a signal binds to a cell (message delivered) and converts it into a specific cellular response

Ligand binds to receptor → induces series of reactions for cell response

Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes

Ligand - things that bind to receptors and trigger signal transduction pathways

Neurotransmitters: SYNAPTIC SIGNALING nervous system ligands, how nerves communicate with target cells thru a synapse, enter synapse through exocytosis, doesn’t travel a far distance in synaptic cleft (ergo local)

Bind to receptors like GPCR (epinephrine), RTK (growth factors), or ligand gated

Hormones: ONLY LONG DISTANCE, sent thru bloodstream

Growth Factors: most important ligand PARACRINE SIGNALING trigger cell division, cause growth and repair. Don’t travel a far distance. Fix damaged parts of the body. Large role if cancer occurs

Local Signaling: animal cells may communicate by direct contact, or cell-cell recognition, info not sent very far

Gap junctions: cells are tightly bound and act as one unit (heart pumping)

Plasmodesmata: rigid cell walls make diffusion difficult between plant cells, they have plasmodesmata tubes instead

Cell-to-Cell Recognition: can determine if self or nonself using glycoproteins

Synaptic signaling- use neurotransmitters for neurons to communicate to target cells

Paracrine signaling- use growth factors, can repair wounds

Affect nearby cells, do not enter bloodstream

Long-distance Signaling:

Released in the bloodstream by endocrine system (hormones)

Every cell in body is exposed to hormone, only cells with receptors respond to the hormone

Target cell is the cell being communicated wit

Growth hormone: grow a lot of cells, growth factors only affect nearby cells, hormones in the bloodstream

RECEPTION

Receptors: specific membrane proteins that receive the ligands and trigger transduction, ligands that bind to ion channel, GPCR, RTK has to be polar

(G protein-coupled receptors) GPCR Receptors: largest family of cell surface receptors, include epinephrine

G-protein normally an inactive protein but activated when ligand binds to it (epinephrine and using GTP), sent on a mission by receptor to trigger a cell response

(Receptor tyrosine kinases) RTK Receptors: Growth factors, any broken receptors associated with cancer

Responds to ligands like growth factors

Causes cell division

Malfunctioning RTKs causes cancer

Phosphorylates relay proteins

Ligand-gated ion channel: acts as a gate when the receptor changes shape, e.g. neurotransmitters

In nervous system: e.g. sodium & calcium channels

Have a gate, and the only way to open it is to have a ligand bind to it, K+, Ca+ or Na+ can enter/leave the cell

Intracellular receptors: proteins found in the cytosol or nucleus of target cells, receives NONPOLAR hormones

Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors

E.g. testosterone, or estrogen (steroids)

Binds to protein in nuclear envelope and initiates transcription

Activated hormone-receptor complex can act as a transcription factor, turning on specific genes

TRANSDUCTION

Protein Kinase: 2nd messengers perform transduction where message is relayed throughout the cell. Proteins that are specialized activated thru phosphorylation “Passing the baton” (relay message), causes a chain

Phosphorylation Cascade: series of activated protein kinases that receive and transport the relay molecule (using ATP) often involving 2nd messengers

Message relayed throughout the cell, prompting a cell response

Using a series of protein kinases using phosphorylation

Responsible for passing the message through the cell using a phosphorylation cascade , passing the relay message as a baton

Second Messenger: anything not a protein kinase that performs transduction/relay the message; water-soluble molecules or ions that spread throughout a cell by diffusion. Participate in pathways initiated by GPCR and RTK.

Cyclic AMP (cAMP)

Most common 2nd messenger

Created using Adenylyl cyclase by taking ATP and cutting off two phosphates (becomes adenosine monophosphate)

E.g. epinephrine binds to GPCR and G protein phosphorylates adenylyl cyclase and makes cAMP and cAMP activates a protein kinase

Ca+++ (calcium ions)

Cell can tightly regulate Ca concentration (active transport) in ER and mitochondria

Can activate IP3 or DAG

IP3

Diacylglycerol (DAG)

RESPONSE

Cell Response: depends on the pathway within the cell leads to regulation of transcription or cytoplasmic activities or “output response”

Many signaling pathways regulate the synthesis of enzymes or other proteins usually by turning genes on or off in the nucleus

Other pathways regulate the activity of enzymes rather than their synthesis

Signal pathways can also affect the overall behavior of a cell, for example, changes in a cell shape

Initiate transcription: begin production of proteins within the cell, control what happens in the cell

E.g. testosterone, estrogen, progesterone

Change cell behavior: tell the cell to do something

E.g. yeast (fungus) cells mating (making shmoos, induce change in cell shape) produce actin microfilaments (for cell movement and shape) to form cortex for changing cell shape (shmoo)

Muscle contractions

Pheromones: externally released ligands for organism-to-organism communication

Activate enzymes: control what chemical reactions the cell is able to perform

Apoptosis (1. DNA mutation, 2. Misfolded protein, 3. Death signal)

Active or suppress genes: triggered by growth factors and hormones

Fine-Tuning of the Response

Amplification of the Signal (and response): enzyme cascades amplify the cell’s response the number of activated products is much greater than in the preceding step

Small amount of ligand create a large response

All of the proteins relaying the message can amplify the response, can activate many enzymes

Specificity of the Response: pathway within the cell dictates the response given from that ligand

Cell can only respond if they have the receptor but the pathway determines what that response is

Efficiency of the Response: increased using scaffolding proteins hold many relay proteins in one location. Have proteins associated with pathway close together to make pathway faster

Termination of the Signal: unbound receptors revert to an inactive state

Specific Responses

Apoptosis: controlled cell death using lysosomes’ hydrolytic proteins (proteases, amylases [carbs], nucleases, etc.) cells in a vesicle the vesicles are taken in by white blood cells and digested

Lysosomal enzymes are released in the cell and break everything down, package everything into vesicles and WBC phagocytosis consumes the vesicles

Release of “death-signal” binds to receptor initiation of phosphorylation cascade and activates nucleases (nucleic acids) and proteases (protein) that break down the cell

Activate enzymes mainly caspase

Reasons: normal development, selectively killing particular cells (finger webbing removal, more space between digits) embryonic development

Triggered by DNA damage (mutation) in the nucleus

Extracellular death ligands (signals)

Protein misfolding in the nucleus (e.g. alzheimer's, parkinson's)

Mutations cause cancer and disease so it’s better to destroy the cell → when things go awry apoptosis is the safeguard

Evolved in early animal evolution and is essential for development and maintenance of all animals

Interference with apoptosis may cause cancer

Caspases are the main proteases (enzymes that cut up proteins that carry out apoptosis)

CELL CYCLE

Interphase: any time the cell is not dividing

G1 (Growth 1): cell spends the bulk of its time, the cell grows and begins normal processes

S (Synthesis): cell begins to prepare for division. DNA replicatescritical to mitosis so both new daughtercells get a full set of DNA

****The chromosomes make copies and are held together by a centromere band, the two copies held are called sister chromatids, those chromatids are identical to each other and are still considered one chromosome, one mitotic chromosome, when the cell divides, the sister chromatids separate and are now separate chromosomes, both daughter cells get one copy and have the same chromosomes as the parent.

If DNA replicates it has to divide, a critical point to decide whether or not it will divide

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