What to Study: Ce ll Co m m u n ica t io n ,

Ap p lica t io n s o f Ce ll Co m m u n ica t io n &

Ce ll Divis io n

Cell Communication, etc: What to Study He re ’s w h a t yo u w ill n e e d t o m a ke su re yo u u n d e rst a n d in o rd e r t o p re p a re fo r o u r e xa m :

● Ce ll Co m m u n ica t ion○ Sig n a l Tra n sd u c t ion P a t h w a ys ○ G p ro t e in lin ke d re ce p t o rs /G p ro t e in s○ P ro t e in kin a se s○ Typ e s o f ce ll s ig n a lin g : p a ra c rin e , a u t o c rin e , e n d o crin e

● Ap p lica t ion s o f Ce ll Co m m u n ica t ion : Bo d y Syst e m s ○ Ho w d o t h e fo llo w in g syst e m s a llo w o rg a n ism s t o

co m m u n ica t e , m a in t a in h o m e o st a s is? ■ Im m u n e■ En d o crin e■ Ne rvo u s

Communication Concepts to Un d e rst a n d

● St ru c t u re o f m o le cu le s a n d t h e re la t ion sh ip t o fu n c t ion

● P h osp h o ryla t ion a n d e n e rg y t ra n sfe r● Me m b ra n e s t ru c t u re a n d fu n c t ion● Ge n e e xp re ssion a n d e n zym e a c t ivit y ● Com m on p roce sse s fo r a ll life

Prokaryote vs Eukaryote Cell SignalingEu ka ryo t e s u se :● G p ro t e in s/G p ro t e in

lin ke d re ce p t o rs ● P ro t e in kin a se s ● En d ocrin e s ig n a lin g

○ Horm on e s● P a ra c rin e s ig n a lin g

○ Im m u n e syst e m ce lls , syn a p t ic t ra n sm ission

● Au t oc rin e s ig n a lin g

P roka ryo t e s u se : ● Qu oru m se n sin g

Quorum Sensing Qu oru m se n sin g is a w a y b a c t e ria ca n com m u n ica t e w it h o t h e r b a c t e ria

● In t e rsp e c ie s com m u n ica t ion

● In t ra sp e c ie s com m u n ica t ion

Presenter

Presentation Notes

A variety of intercellular and intracellular signal transmissions mediate gene expression.

Core Process: Signal TransductionLike a p h on e ca ll:● Re ce p t ion● Tra n sd u c t ion● Re sp on se

G protein linked receptors use second m e sse n g e rs a n d p h o sp h o ryla t io n ca sca d e s

Sa m e id e a : re ce p t ion , t ra n sd u c t ion a n d re sp on se

Me ssa g e is a m p lifie d so fe w e r s ig n a lin g m o le cu le s a re n e e d e d

Like se n d in g a vira l t e xt o r Tw e e t t h a t g e t s re t w e e t e d

Epinephrine signaling: An e xa m p le o f a G-p ro t e in lin ke d p a t h w a y

Ut ilize d in “fig h t o r flig h t ” re sp on se

He lp s t o m ob ilize g lu cose d u rin g t im e s o f s t re ss

Protein Kin a se s● Kin a se s

p h osp h o ryla t e o t h e r m o le cu le s t o e n a b le t h e m t o d o w ork

● Sig n a lin g ca sca d e s a re a lso in vo lve d : t h in k re t w e e t s!

Types of Eukaryote Signaling: En d o crin e

En d ocrin e s ig n a lin g : t h e ce ll se c re t e s a lig a n d m o le cu le t h a t t ra ve ls t h rou g h t h e b od y t o a t a rg e t ce ll

Types of Eukaryote Signaling: P a ra c rin e

P a ra c rin e s ig n a lin g : t h e ce ll se c re t e s a lig a n d t h a t b in d s t o n e a rb y ce lls

Types of Eukaryote Signaling: Au t o c rin e

Au t oc rin e s ig n a lin g : t h e ce ll se c re t e s a lig a n d t h a t b in d s t o it s ow n m e m b ra n e

Application of Cell Communication: Im m u n e Syst e m

P la n t s h a ve hypersensitive response● P a t h og e n s t rig g e r

re le a se o f ch e m ica ls t h a t d e st roy in fe c t e d ce lls a n d t h e a d ja ce n t ce lls

● Not e t h e u se o f STP s h e re

Application of Cell Communication: Im m u n e Syst e m

Specific immune response● Tw o t yp e s

○ Ce ll m e d ia t e d ○ Hu m ora l

● Not e ro le o f He lp e r T ce ll: coo rd in a t e s b o t h re sp on se s

Application of Cell Communication: Im m u n e Syst e m

Antibodies and Antigens● An t ib od ie s: p rod u ce d b y

p la sm a B ce lls ● An t ig e n s: p re se n t on

su rfa ce o f p a t h og e n s, ce lls● Bin d in g s it e on a n t ib od y

fit s sh a p e o f a n t ig e n

Application of Cell Communication: Ne rvo u s Syst e m

Transmission of information between neurons happens at synapses: kn o w w h a t h a p p e n s, ro le o f n e u ro t ra n sm it t e rs

AP Biology

Cell Differentiation Demands Coordination

Different tissues & organs develop, grow, and repair at different rates

◆ This is critical for normal growth, development & maintenance▪ Timing of cell division must be right▪ Rates of cell division are unique▪ Not all cells can have the

same Cell Cycle

AP Biology

G2

S G1

Mmetaphase

prophaseanaphase

telophase

interphase (G1, S, G2phases)mitosis (M)cytokinesis (C)

C

▪ Embryos◆ cell cycle < 20 minute

▪ Skin Cells◆ Divide frequently throughout life◆ 12-24 hours cycle

▪ Liver Cells◆ Retain ability to divide, but keep it in reserve◆ Divide once every year or two

▪ Mature Nerve Cells & Muscle Cells◆ Do not divide at all after maturity◆ Permanently in G0

Frequency of Cell Division Varies by Type

AP Biology

Phases of the Cell Cycle

AP Biology

Phases of the Cell Cycle● The mitoticphase alternates with interphase:

G1→ S → G2 → mitosis → cytokinesis● Interphase(90 % of cell cycle)

▪ G1Phase: cell grows and carries out normal functions

▪ S Phase: duplicates chromosomes▪ G2 Phase: prepares for cell division

● M Phase(mitotic)▪ Mitosis: nucleus divides (PMAT)

AP Biology

Mitosis : Prophase → Metaph ase →An aph ase → Teloph ase

PMAT not IPMAT!

Cytokinesis in animal vs. plant cells

AP Biology

Checkpoint Control System▪ Checkpoints

◆ Cell cycle controlled by STOP & GOchemical signals at critical points

◆ Signals indicate if key cellular processes have been completed correctly▪ External- Growth Factors▪ Internal- Promoting Factors

• Cyclins

AP Biology

3 Major Checkpoints “Ask” Critical QuestionsG1/S

◆ Can DNA synthesis begin?G2/M

◆ Has DNA synthesis been completed correctly?

◆ Commitment to MitosisSpindle Checkpoint

◆ Are all chromosomes attached to spindle?

AP Biology

“Go-ahead” Protein signals▪ Protein signals that promote cell

growth & division◆ External “Go-ahead”Signals

▪ “Growth Factors”◆ Internal “Go-ahead”Signals

▪ “Promoting Factors”▪ Primary Mechanism of Control

◆ Phosphorylation-▪ adds phosphate groups to target

AP Biology

“Go-ahead” Protein signals▪ Protein signals that promote cell growth & division

◆ External “Go-ahead”Signals▪ “Growth Factors”

◆ Internal “Go-ahead”Signals▪ “Promoting Factors”

▪ Primary Mechanism of Control◆ Phosphorylation-

▪ adds phosphate groups to target▪ Kinase- a phosphorylating enzyme▪ either activates or inactivates cell signals

AP Biology

Promoting Factors▪ Internal Protein Signals

◆ cyclins▪ regulatory proteins▪ levels cycle in the cell

◆ Cdks▪ cyclin-dependent kinases▪ phosphorylates cellular proteins

• activates or inactivates proteins◆ Cdk-cyclin complex

▪ triggers passage through different stages of cell cycle▪ ex. Maturation Promoting Factor

activated Cdk

inactivated Cdk

AP Biology

Cyclin & Cyclin-dependent kinases▪ CDKs & cyclin drive cell from

one phase to next in cell cycle

◆ proper regulation of cell cycle is so key to life that the genes for these regulatory proteins have been highly conservedthrough evolution

◆ the genes are basically the same in yeast, insects, plants & animals (including humans)

AP Biology

Specific Cyclins and CDKs promote progression through specific phases

AP Biology

Cdk / G1

cyclin

Cdk / G2cyclin (MPF)G2

S

G1

CM

G2 / M checkpoint

G1 / S checkpoint

APC

Active Inactive

ActiveInactiveInactive

Active

mitosiscytokinesis

MPF = Mitosis Promoting FactorAPC = Anaphase Promoting Comple

• Replication completed• DNA integrity

Chromosomes attached at metaphase plate

Spindle checkpoint

• Growth factors• Nutritional state of cell• Size of cell

AP Biology

Growth Factors and Cancer▪ Growth factors can create cancers

◆ proto-oncogenes▪ normally activates cell division

• growth factor genes • become oncogenes (cancer-causing) when mutated

▪ if switched “ON” can cause cancer▪ example: RAS (activates cyclins)

◆ tumor-suppressor genes▪ normally inhibits cell division

if ithd “OFF”

AP Biology

Cancer & Cell Growth▪ Cancer is essentially a failure

of cell division control◆ unrestrained, uncontrolled cell growth

▪ What control is lost?◆ lose checkpoint stops◆ gene p53 plays a key role in G1/S restriction point

▪ p53 protein halts cell division if it detects damaged DNA • options:

■ stimulates repair enzymes to fix DNA ■ forces cell into G0 resting stage■ keeps cell in G1 arrest ■ causes apoptosis of damaged cell

▪ ALL cancers have to shut down p53 activity

p53 discovered at Stony Brook by Dr. Arnold Levine

p53 is theCell CycleEnforcer

AP Biology

DNA damage is causedby heat, radiation, or chemicals.

p53 allows cellswith repairedDNA to divide.

Step 1

DNA damage iscaused by heat,radiation, or chemicals.

Step 1 Step 2

Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.

Step 3p53 triggers the destruction of cells damaged beyond repair.

ABNORMAL p53

NORMAL p53

abnormalp53 protein

cancercellStep 3The p53 protein fails to stop

cell division and repair DNA.Cell divides without repair todamaged DNA.

Cell division stops, and p53 triggers enzymes to repair damaged region.

Step 2

DNA repair enzymep53protein p53

protein

p53 — master tumor suppressor gene