Read Microsoft PowerPoint - NVC_Biol_120_11_Communication [Compatibility Mode] text version

10/15/2011

Chapter 11 ­ Cell Communication

Outline

I. Cell Signaling II. Forms of cell signaling III. Quick review of cell membrane IV. Cell Surface Receptors

I. G-protein Coupled Receptors II. Tyrosine Kinase Receptors III. Ligand-Gated Ion Channels

V. Intracellular Receptors I. Down regulation II. Apoptosis

Figure 11.1

Overview: Cellular Messaging

Cell-to-cell communication is essential for both multicellular and unicellular organisms Biologists have discovered some universal mechanisms of cellular regulation Cells most often communicate with each other via chemical signals For example, the fight-or-flight response is triggered by a signaling molecule called epinephrine

© 2011 Pearson Education, Inc.

Evolution

Fossil record indicate that one celled bacteria were present on earth 3.5 billion years ago But it took another 2.5 billions years for multicellular organisms to appear in the fossil record What took so long for multicellular life to evolve?

Evolution of Signaling

Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling molecules allows bacteria to sense local population density

© 2011 Pearson Education, Inc.

1

10/15/2011

Local and Long-Distance Signaling

Cells in a multicellular organism communicate by chemical messengers

Figure 11.4

Plasma membranes

Gap junctions between animal cells

Plasmodesmata between plant cells

Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells In local signaling, animal cells may communicate by direct contact, or cell-cell recognition

(a) Cell junctions

(b) Cell-cell recognition

© 2011 Pearson Education, Inc.

Local and Long-Distance Signaling

In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances In long-distance signaling, plants and animals use chemicals called hormones The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal

Forms of Signaling

1. Gap Junctions 2. Autocrine

A cell secretes a molecule that binds back onto its own receptor Local mediators Neurotransmitters, released into synaptic cleft Hormones, secreted into the bloodstream

3. Paracrine

4. Synaptic ­ Nerve cell signal transmission 5. Endocrine

© 2011 Pearson Education, Inc.

Figure 11.5a

Figure 11.5b

Long-distance signaling Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter. Endocrine cell Blood vessel

Secreting cell

Secretory vesicle

Neurotransmitter diffuses across synapse. Target cell specifically binds hormone. Target cell is stimulated. (b) Synaptic signaling

Hormone travels in bloodstream.

Local regulator diffuses through extracellular fluid. (a) Paracrine signaling

(c) Endocrine (hormonal) signaling

2

10/15/2011

The Three Stages of Cell Signaling

Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes

Reception Transduction Response

Animation: Overview of Cell Signaling

Right-click slide / select "Play"

© 2011 Pearson Education, Inc. © 2011 Pearson Education, Inc.

Figure 11.6-1

Figure 11.6-2

EXTRACELLULAR FLUID 1 Reception Receptor

CYTOPLASM Plasma membrane

EXTRACELLULAR FLUID 1 Reception Receptor

CYTOPLASM Plasma membrane 2 Transduction

Relay molecules in a signal transduction pathway Signaling molecule Signaling molecule

Figure 11.6-3

Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell

EXTRACELLULAR FLUID 1 Reception Receptor

CYTOPLASM Plasma membrane 2 Transduction 3 Response

Signal transduction usually involves multiple steps Multistep pathways can amplify a signal: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response

Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule

© 2011 Pearson Education, Inc.

3

10/15/2011

Fig. 9.8.b

Signal Transduction Pathways

The molecules that relay a signal from receptor to response are mostly proteins Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a shape change in a protein

© 2011 Pearson Education, Inc.

Protein Phosphorylation

In many pathways, the signal is transmitted by a cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation

Protein Dephosphorylation

Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required

© 2011 Pearson Education, Inc.

© 2011 Pearson Education, Inc.

Figure 11.10

Figure 11.10a

Signaling molecule

Activated relay molecule

Inactive protein kinase 1

Receptor

Activated relay molecule

Inactive protein kinase 1

Active protein kinase 1 Inactive protein kinase 2

Pi ATP ADP PP

Active protein kinase 1 Inactive protein kinase 2

ATP ADP

Active protein kinase 2

ATP ADP

P

PP Pi

Active protein kinase 2

ATP ADP

P

Inactive protein kinase 3

Pi

Inactive protein kinase 3

Active protein kinase 3

ATP ADP P P

PP

Pi

PP

Active protein kinase 3

ATP ADP

P

Inactive protein

Inactive protein

Active protein Cellular response

Pi

P

Pi

PP

PP

Active protein

4

10/15/2011

Fig. 9.3

Which type of ligand would bind to a receptor in the plasma membrane 1. Water soluble 2. Lipid soluble

50% 50%

1

Copyright © 2009 Pearson Education, Inc.

2

The following can freely pass through a membrane: 1. Ions 2. Hydrophobic molecules 3. hydrophillic molecules 4. Ions and hydrophilic molecules

Copyright © 2009 Pearson Education, Inc.

Fig. 9.1

25%

25%

25%

25%

1

2

3

4

Reception: A signaling molecule binds to a receptor protein, causing it to change shape

The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins

© 2011 Pearson Education, Inc.

Receptors in the Plasma Membrane

Most water-soluble signal molecules bind to specific sites on receptor proteins that span the plasma membrane = cell surface receptors There are three main types of membrane receptors

G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors

© 2011 Pearson Education, Inc.

5

10/15/2011

Receptors in the Plasma Membrane - GPCRs

G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors A GPCR is a plasma membrane receptor that works with the help of a G protein

Figure 11.7a

Signaling molecule binding site

Segment that interacts with G proteins G protein-coupled receptor

© 2011 Pearson Education, Inc.

G-Coupled Receptor

G Proteins

Trimeric GTP-binding protein = G Proteins G Proteins are either in the active or inactive state Active state has GTP bound When the ligand binds the G-protein Coupled Receptor, this causes a change in shape, that activates the G Protein This starts a chain of events that involve intracellular mediators = secondary messengers

Figure 11.7b

Trimeric G Proteins

Activated receptor Signaling molecule Inactive enzyme

G protein-coupled Plasma membrane receptor

G Proteins are composed of three proteins:

and and subunits

GDP

CYTOPLASM 1

GTP GDP

G protein (inactive)

Enzyme 2 Activated enzyme

GDP

GTP

When the G Protein is activated (GTP is bound) the subunit (with GTP) goes one way and the and go together another way.

Pi

GTP

GDP

3

Cellular response

4

and are active when they are not attached to the subunit the subunit has GTPase activity

6

10/15/2011

GTPase activity in G proteins

The G protein is active only when it has GTP bound to it. The G protein has GTPase activity, which means it will automatically hydrolyze a phosphate and have GDP bound. This way it inactivates itself automatically This GTPase activity is enhanced by GTPase Activating Proteins (GAPs)

Fig. 9.11

GPCR video

http://youtu.be/V_0EcUr_txk

Small Molecules and Ions as Second Messengers

The extracellular signal molecule (ligand) that binds to the receptor is a pathway's "first messenger" Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by GPCRs and RTKs Cyclic AMP and calcium ions are common second messengers

© 2011 Pearson Education, Inc.

Figure 11.11a

Cyclic AMP

· Cyclic AMP (cAMP) is one of the most widely used second messengers · Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal

ATP

Adenylyl cyclase

Pyrophosphate

P Pi

cAMP

© 2011 Pearson Education, Inc.

7

10/15/2011

Figure 11.11b

Figure 11.12

First messenger (signaling molecule such as epinephrine) G protein Adenylyl cyclase

Phosphodiesterase

H2O

G protein-coupled receptor

GTP ATP cAMP

H2O

Second messenger Protein kinase A

cAMP

AMP

Cellular responses

cAMP Pathway

1. A ligand binds to the G-protein Coupled Receptor (GPCR). 2. The binding of the ligand (hormone) activates the GPCR. 3. The active GPCR is able to bind the Gprotein 4. The G-protein ejects a GDP and accepts a GTP molecule. The G-protein is now active 5. The subunit of the G-protein with the GTP disassociates from the and subunits 6. The subunit of the G-protein with the GTP goes to adenylyl cyclase and activates it 7. The active adenylyl cyclase transforms ATP into cAMP 8. cAMP activates a protein kinase A (PKA) 9. cAMP is inactivated by phosphodiesterases 10. The PKA phosphorylates proteins 11. The phosphorylated proteins are now active and can change the cell activity 12. The g-protein with GTP bound will hydrolyze the phosphate from GTP, now has GDP bound and is inactive. It will reform with the and subunits and this inactivates them

Fig. 9.13

Fig. 9.16

8

10/15/2011

Figure 11.16 Reception Binding of epinephrine to G protein-coupled receptor (1 molecule)

Gene transcription by cAMP

The cAMP pathway can also activate the transcription of specific genes The protein kinase A (PKA) activated by cAMP can turn on transcription of DNA using a CRE-binding protein (cAMP response element)

Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose 1-phosphate (108 molecules)

Examples of Hormone induced responses mediated by cAMP

Target Tissue Adrenal Cortex Ovary Muscle Bone Heart Liver Kidney Fat Hormone Major Response ACTH Cortisol Secretion LH Progesterone secretion Adrenaline Glycogen breakdown Parathyroid Bone reabsorption hormone (PTH) Adrenaline Increase heart rate Glucagon Glycogen breakdown Vasopressin Water reabsorption Adrenaline, Triglyceride ACTH, glucagon breakdown

Animation: Signal Transduction Pathways

Right-click slide / select "Play"

© 2011 Pearson Education, Inc.

Calcium Ions and Inositol Triphosphate (IP3)

Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration

Figure 11.13

EXTRACELLULAR FLUID Ca2 pump Mitochondrion

Plasma membrane

ATP

Nucleus CYTOSOL Ca2 pump Ca2 pump Endoplasmic reticulum (ER)

ATP

Key

© 2011 Pearson Education, Inc.

High [Ca2 ]

Low [Ca2 ]

9

10/15/2011

Calcium Ions IP3 and DAG

A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers

IP3/DAG Pathway

Remember that the plasma membrane is a double layer of phospholipids. It is a mixture of different phospholipids. One of the phospholipids in the membrane is PIP2 in the membrane.

© 2011 Pearson Education, Inc.

Figure 11.14-1

EXTRACELLULAR FLUID

Signaling molecule (first messenger) G protein DAG

GTP

G protein-coupled receptor

Phospholipase C

PIP2 IP3 (second messenger)

IP3-gated calcium channel

Endoplasmic reticulum (ER)

Ca2

CYTOSOL

Figure 11.14-2

Figure 11.14-3

EXTRACELLULAR FLUID

Signaling molecule (first messenger) G protein DAG

GTP

EXTRACELLULAR FLUID

Signaling molecule (first messenger) G protein DAG

GTP

G protein-coupled receptor

Phospholipase C

PIP2 IP3 (second messenger)

G protein-coupled receptor

Phospholipase C

PIP2 IP3 (second messenger)

IP3-gated calcium channel

IP3-gated calcium channel

Endoplasmic reticulum (ER)

Ca2 Ca2 (second messenger)

Endoplasmic reticulum (ER)

Ca2 Ca2 (second messenger)

Various proteins activated

Cellular responses

CYTOSOL

CYTOSOL

10

10/15/2011

Fig. 9.14

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Ca2+

Ca2+

Ca2+ Inactive protein Calmodulin

Calmodulin

Active protein

a.

b.

IP3 and DAG Pathway

1. A ligand binds to the G-protein Coupled Receptor (GPCR). 2. The binding of the ligand (hormone) activates the GPCR. 3. The active GPCR is able to bind the Gprotein 4. The G-protein ejects a GDP and accepts a GTP molecule. The G-protein is now active 5. The subunit of the G-protein with the GTP disassociates from the and subunits

6. The subunit of the G-protein with the GTP bound goes to phospholipase C (PLC) and activates it 7. The active PLC splits the phospholipid PIP2 into two parts: IP3 and DAG. 8. IP3 causes the endoplasmic reticulum to release Ca++ 9. Ca ++ binds to proteins like calmodulin 10. Calmodulin with Ca ++ bound activates other proteins

11. DAG activates protein kinase C (PKC), Ca++ is needed for the activation 12. Active PKC phosphorylates proteins 13. Phosphorylated proteins are active and alter cell activity 14. The g-protein with GTP bound will hydrolyze the phosphate from GTP, now has GDP bound and is inactive. It will reform with the and subunits and this inactivates them 15. The cell stores Ca++ in organelles and pumps it out of the cell

Cellular responses mediated by IP3

Target Tissue Liver Pancreas Smooth Muscle Mast cells Blood Platelets

Signaling Molecule Vasopressin Acetylcholine Acetylcholine Antigen Thrombin

Major Response Glycogen Breakdown Amylase secretion Contraction Histamine Secretion Aggregation

11

10/15/2011

Enzyme-Linked Cell Surface Receptors

Receptor tyrosine kinases (RTKs)

Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Abnormal functioning of RTKs is associated with many types of cancers

© 2011 Pearson Education, Inc.

Receptor tyrosine kinases (RTK)

Phosphorylates tyrosine amino acids on signaling proteins

Receptor Serine/threonine kinases

Phosphorylates serine or threonine amino acids on signaling proteins

Receptor Tyrosine Kinase

These receptors just cross the plasma membrane once ­ single transmembrane proteins RTKs are dimers ­ it takes two RTKs to function Binding of the ligand causes two RTKs to come together and link to form a dimer = dimerize

Receptor Tyrosine Kinase

When the two receptors link together, they now have enzyme activity They phosphorylate tyrosine residues on each other = autophosphorylation This requires ATP

Receptor Tyrosine Kinase Ligands

Figure 11.7c

Signaling molecule (ligand) helix in the membrane

Ligand-binding site Signaling molecule

Examples of ligands for receptor tyrosine kinases:

Insulin Growth hormone Erythropoietin

1

Tyrosines

Tyr Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

Tyr Tyr Tyr

CYTOPLASM

Receptor tyrosine kinase proteins (inactive monomers)

Dimer 2 Activated relay proteins

Tyr Tyr Tyr

Tyr Tyr Tyr

P Tyr P Tyr

Tyr P Tyr P Tyr P

P Tyr P Tyr P Tyr

Tyr P Tyr P Tyr P

Cellular response 1 Cellular response 2

6

ATP

6 ADP

P Tyr

3

Activated tyrosine kinase regions (unphosphorylated dimer)

Fully activated receptor tyrosine kinase (phosphorylated dimer)

4

Inactive relay proteins

12

10/15/2011

Fig. 9.7

MAP Cascades

Mitogen-activated protein kinases (MAP) Mitogens are important in normal cell division MAP kinases are a series of protein kinases that phosphorylate other protein kinases Ending in a cellular response including gene transcription These cascades amplify the response

MAP Cascades

The process starts with a growth factor binding to a RTK RTK dimerizes and autophorylates The activated RTK bind activator proteins The activator proteins (GRB2 and SOS) activate a GTP-binding proteins (G protein) called Ras When Ras is activated, it releases GDP and accepts GTP Ras activates MKKK, which activates MKK......

Fig. 9.8.a

Fig. 9.8.b

13

10/15/2011

Fig. 9.10

Figure 11.15

Growth factor Receptor

Reception

Phosphorylation cascade

Transduction

CYTOPLASM

Inactive transcription factor DNA

Active transcription factor

P

Response

Gene NUCLEUS mRNA

Summary of RTK/Ras/MAP Pathway

1. Two ligands binds to two RTKs (one ligand/receptor) 2. The two RTK dimerize and phosphorylate each other, activating each other 3. The active RTKs activate a protein that stimulates Ras to eject GDP and accept GTP 4. The now active Ras activates the MAP kinase cascade until the MAP kinase is activated 5. The MAP kinase activates proteins which leads to cellular activity. 6. Ras will automatically inactivate by dephosphorylating the GTP to GDP

14

10/15/2011

Ligand-gated ion channel

A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

Figure 11.7d

1 Gate closed Ions

2 Gate open

3 Gate closed

Signaling molecule (ligand)

Plasma Ligand-gated membrane ion channel receptor

Cellular response

© 2011 Pearson Education, Inc.

Intracellular Receptors

Intracellular receptor proteins are found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes

© 2011 Pearson Education, Inc.

Intracellular Receptors

Lipid soluble and small signaling molecules bind to receptors located inside the cell. Intracellular receptors are located in the cytosol or the nucleus The intracellular receptors in the cytosol will bind with the ligand, the binding will cause the receptor/ligand complex to travel to the nucleus.

Examples of Intracellular Receptors

Steroid hormones

Estrogen, testosterone, cortisol Effects gene expression

Steroid Hormone Intracellular Receptors

These hormones cross the plasma membrane and bind to an intracellular receptor in the cytosol The binding of the ligand to the receptor causes the ligand/receptor to go to the nucleus The ligand/receptor regulates gene expression

Nitric Oxide (gas)

Binds to receptor that is an enzyme = guanylyl cyclase

15

10/15/2011

Intracellular Receptors

Intracellular Receptors

Intracellular receptors have three regions:

Ligand binding domain DNA binding domain Transcription activating domain

Prior to the ligand binding, the receptor may have proteins that block the DNA binding domain. The binding of the ligand signals the receptor to go the nucleus and allow the receptor to bind to the DNA

Fig. 9.5

Figure 11.9-1

Hormone (testosterone)

EXTRACELLULAR FLUID

Receptor protein

Plasma membrane

DNA

NUCLEUS

CYTOPLASM

Figure 11.9-2

Figure 11.9-3

Hormone (testosterone)

EXTRACELLULAR FLUID

Hormone (testosterone)

EXTRACELLULAR FLUID

Receptor protein

Plasma membrane

Receptor protein

Plasma membrane

Hormonereceptor complex

Hormonereceptor complex

DNA

DNA

NUCLEUS

NUCLEUS

CYTOPLASM

CYTOPLASM

16

10/15/2011

Figure 11.9-4

Figure 11.9-5

Hormone (testosterone)

EXTRACELLULAR FLUID

Hormone (testosterone)

EXTRACELLULAR FLUID

Receptor protein

Plasma membrane

Receptor protein

Plasma membrane

Hormonereceptor complex

Hormonereceptor complex

DNA mRNA mRNA

DNA

NUCLEUS

NUCLEUS

New protein

CYTOPLASM

CYTOPLASM

Nuclear and Cytoplasmic Responses

Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities

Figure 11.17

RESULTS

Wild type (with shmoos)

Fus3 Shmoo projection forming

formin

The response may occur in the cytoplasm or in the nucleus Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule in the signaling pathway may function as a transcription factor

CONCLUSION 1 Mating factor activates receptor. Mating factor G protein-coupled receptor

Formin P Fus3 Actin subunit

GDP

GTP 2 G protein binds GTP and becomes activated. Phosphorylation cascade

P

Fus3

Fus3

Formin Formin P 4 Fus3 phosphorylates Microfilament formin, activating it. 5 Formin initiates growth of microfilaments that form the shmoo projections.

P 3 Phosphorylation cascade activates Fus3, which moves to plasma membrane.

© 2011 Pearson Education, Inc.

Fine-Tuning of the Response

There are four aspects of fine-tuning to consider

Amplification of the signal (and thus the response) Specificity of the response Overall efficiency of response, enhanced by scaffolding proteins Termination of the signal

Signal Amplification

Enzyme cascades amplify the cell's response At each step, the number of activated products is much greater than in the preceding step

© 2011 Pearson Education, Inc.

© 2011 Pearson Education, Inc.

17

10/15/2011

The Specificity of Cell Signaling and Coordination of the Response

Different kinds of cells have different collections of proteins These different proteins allow cells to detect and respond to different signals Even the same signal can have different effects in cells with different proteins and pathways Pathway branching and "cross-talk" further help the cell coordinate incoming signals

Figure 11.18

Signaling molecule

Receptor

Relay molecules

Activation or inhibition

Response 1 Cell A. Pathway leads to a single response.

Response 2

Response 3

Response 4 Cell C. Cross-talk occurs between two pathways.

Response 5 Cell D. Different receptor leads to a different response.

Cell B. Pathway branches, leading to two responses.

© 2011 Pearson Education, Inc.

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes

Scaffolding proteins are large relay proteins to which other relay proteins are attached Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway In some cases, scaffolding proteins may also help activate some of the relay proteins

© 2011 Pearson Education, Inc.

Figure 11.19

Signaling molecule

Plasma membrane

Receptor Three different protein kinases Scaffolding protein

Termination of the Signal

Inactivation mechanisms are an essential aspect of cell signaling If ligand concentration falls, fewer receptors will be bound Unbound receptors revert to an inactive state

Receptor Internalization

One way this pathway is inactivated is through Ras GTPase activity Another way this pathway is down-regulated is internalization of the receptors We will come back to this at the end of the lecture

© 2011 Pearson Education, Inc.

18

10/15/2011

Controlling Cell Signaling

To control cell signaling:

1. 2. 3. 4. The G-proteins have GTPase activity Ligand levels fall Ca++ is sequestered There are phosphatases that inactivate the proteins that were activated by phosphorylation 5. Phosphodiesterases 6. Receptors are internalized

http://biochemistry.utoronto.ca/brown/mgy425/egan_tk_ras_2009.ppt#68

Apoptosis integrates multiple cell-signaling pathways

Apoptosis is programmed or controlled cell suicide Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells

Figure 11.20

2 m

Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells

19

10/15/2011

Apoptotic Pathways and the Signals That Trigger Them

Mitochondria release cytochrome C Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by

An extracellular death-signaling ligand DNA damage in the nucleus Protein misfolding in the endoplasmic reticulum

© 2011 Pearson Education, Inc.

Apoptotic Pathways

Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals Apoptosis may be involved in some diseases (for example, Parkinson's and Alzheimer's); interference with apoptosis may contribute to some cancers

© 2011 Pearson Education, Inc.

Figure 11.22

Apoptosis video

Florescent labeled Death ligand

Interdigital tissue

Cells undergoing apoptosis

Space between 1 mm digits

Important Concepts

Know the vocabulary covered in this lecture Know examples of signaling molecules Know the forms of cell signaling Know the main classifications of signaling receptors, what are the main differences and what type of ligands generally bind these receptors Understand how intracellular receptors work, what are the steps from the binding of a ligand to the cellular activity and what type of activity is regulated by intracellular receptors.

Important Concepts

Know the three domains of intracellular receptors Know the classes of Cell Surface Receptor Proteins Understand how protein kinases work, what do they do? Know the properties of RTKs. Be able to describe the steps of how the receptors regulate cellular activity What is the benefit of having kinase cascades?

20

10/15/2011

Important Concepts

Know the examples of ligands for the receptors Be able to describe how cellular activity is regulated by the cAMP pathway, starting with the binding of a ligand to the GCPR, including how the g-protein is inactivated Know examples of a cellular response mediated by cAMP Understand the apoptotic pathways and how they are triggered

Important Concepts

Be able to describe the steps of how cellular activity is effected by the IP3 and DAG pathway, starting with the binding of a ligand to the GCPR, including how the g-protein is inactivated Know examples of cellular responses mediated by IP3 How are cell signaling pathways controlled What are differences and similarities between Gprotein couple receptors, enzyme linked receptors (like RTK) and intracellular receptors

21

Information

Microsoft PowerPoint - NVC_Biol_120_11_Communication [Compatibility Mode]

21 pages

Find more like this

Report File (DMCA)

Our content is added by our users. We aim to remove reported files within 1 working day. Please use this link to notify us:

Report this file as copyright or inappropriate

661678


You might also be interested in

BETA
Name_______________________Period___________
Normal
The Impact of an Interactive, Computer Animation-Based Pharmacology Tutorial on Second Year Pharmacy Students' Academic Performance
Layout 1