Cell Signaling

Apoptosis, which can be induced by signals from other cells, is the process by which cells do which of the following?

A) Move to other parts of the cell (migrate).B) Take on different shapes (morphology)C) Express different genes to take on their final function.D) Kill themselves through programmed cell deathE) Eat (phagocytose) other cells

• Cell communication is the process of cells detecting and responding to signals in the extracellular environment

• Needed to coordinate cellular activities in a multicellular organism

• Apoptosis is caused by signals that intentionally cause a cell to die

Why Cell Signaling?

• Cell communication or cell signaling involves incoming and outgoing signals

• Signals are agents that influence the properties of cells– cAMP– Growth Factors– Hormones

• Signals affect the conformation of a receptor (ie a membrane protein) leading to a response inside the cell

Why Cell Signaling?

Why do cells need to respond to signals?

1. Need to respond to a changing environment– Adaptation or a cellular response is critical for

survival– Glucose acts as a signal to yeast cells to increase

number of glucose transporters and enzymes allowing efficient uptake and use of glucose

Why do cells need to respond to signals?

2. Cells need to communicate with each other– Cell-to-cell communication• Auxin is a signaling molecule transmitted from cell to

cell and inhibited by the light

Five Modes of Cell Communication

1. Direct intercellular signaling– Cell junctions allow signaling molecules to pass

from one cell to another.2. Contact-dependent signaling– Some molecules are bound to the surface of cells

and serve as signals to the cell coming in contact with them.

3. Autocrine signaling– Cells secrete signaling molecules that bind to their

own cell surface or neighboring cells of the same type.

4. Paracrine signaling– Signal does not affect cell secreting the signal

but does influence cells in close proximity (synaptic signaling).

5. Endocrine signaling– Signals (hormones) travel long distances and are

usually longer lasting.

Five Modes of Cell Communication (cont)

Five Modes of Cell Communication

3 stages of cell signaling

1. Receptor activation– Signaling molecule binds to receptor

2. Signal transduction/amplification– Activated receptor stimulates sequence of

changes- signal transduction pathway– This can also be used to amplify the signal

3. Cellular response– Several different responses• Alter activity of 1 or more enzymes• Alter structural protein function• Change gene expression– transcription factor

Ligand

• Signaling molecule• Binds noncovalently to receptor with high

degree of specificity• Binding and release between receptor and

ligand relatively rapid• Ligands alter receptor structure-

conformational change• Once a ligand is released, the receptor is no

longer activated

Cell surface receptors

1. Enzyme-linked receptors– Extracellular domain binds signal – Causes intracellular domain to become

functional catalyst– Most are protein kinases

G-protein coupled receptors (GPCR)

2. G-protein coupled receptors (GPCR)– Found in all eukaryotes, common in animals– 7 transmembrane segments– Activated receptor binds to G protein– Releases GDP and binds GTP instead– GTP causes G protein to disassociate– α subunit and β/γ dimer interact with other

proteins in a signaling pathway

3. Ligand-gated ion channels– Plant and animal cells– Ligand binding causes ion channels to open and

ions to flow through the membrane– Animals- signals between nerve and muscle cells or

between 2 nerve cells

4. Receptor tyrosine kinases (RTKs)

• Category of enzyme-linked receptors found in animals

• Recognize various types of signaling molecules– Growth factor – hormone that acts to stimulate

cell growth or division• Epidermal Growth Factor (EGF)– Stimulates epidermal cells to divide

Epidermal Growth Factor Receptor Pathway

Question 5

Receptor tyrosine kinases are found in which of the following?

A) BacteriaB) ArchaeaC) AnimalsD) PlantsE) All of the above

Second Messengers

• Signals binding to cell surface are first messenger

• Many signal transduction pathways lead to production of second messengers– Relay signals inside cells– Examples• cAMP• Ca2+

• Diacylglycerol and inositol triphosphate

Signal transduction via cAMP• Cyclic adenosine monophosphate • Signal binding to GPCR activates G protein to

bind GTP causing dissociation• α subunit binds to adenylyl cyclase stimulating

synthesis of cAMP

Norepinephrine is a hormone that is released into the blood when the adrenal gland is stimulated by the sympathetic preganglionic neurons. What type of signaling effect is does this represent?

A) EndocrineB) ParacrineC) SynapticD) Contact Dependent

Signal transduction via cAMP• One effect of cAMP is to activate protein kinase A

(PKA)• Activated catalytic PKA subunits phosphorylates

specific cellular proteins• When signaling molecules no longer produced,

eventually effects of PKA reversed

Signal transduction via cAMP

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cAMP has 2 advantages

1. Signal amplification– Binding of signal to single receptor can cause the

synthesis of many cAMP that activate PKA, each PKA can phosphorylate many proteins

2. Speed– A substantial amount of cAMP can be made

within 20 seconds after addition of eipnepherine

Signal amplification via cAMP

Hormonal signaling

• Type of cellular response caused by a given signaling molecule depends in the type of cell responding to the signal

• Variation in response determined by types of proteins that each cell makes

A cell’s response to hormones and other signaling molecules depends

on which proteins it makes

• One hormone causes different effects in different cell types

• Differential gene expression- all cells contain the same genome but only express particular parts

• Can effect cellular response in a variety of ways– Receptor not expressed, different receptors for same

signal, different affinities for signal, signal transduction pathways different, protein expression different

Epinephrine example

• Fight-or-flight hormone• Different effects throughout body• Stimulates heart muscle cells to beat faster• Caffeine inhibits phosphodiesterase– Enzyme removes cAMP once a signaling molecule is

no longer present– Inhibition causes cAMP to persist for longer so heart

beats faster

Cell-Cell Junctions

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Anchoring junctions (animal cell)• Attach cells to each other and to the ECM• Rely on cell adhesion molecules (CAM)– Cadherin and integrin

• 4 main categories1. Adherins junctions2. Desmosomes3. Hemidesmosomes 4. Focal adhesions

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Tight junctions in animals• Or occluding junctions• Forms tight seal between adjacent cells• Prevents ECM from leaking between cells• Tight junctions – Made by occludin and claudin– Bind to each to form tight seal– Not mechanically strong, not bound to cytoskeleton

Tight junctions in animals

Gap junctions in animals• Small gap between plasma membranes of cells at

junction• Six connexin proteins in one cell align with six

connexin proteins in an adjacent cell to form a connexon

• Connexon allows passage of ions and small molecules

• Allow adjacent cell to share metabolites and directly signal each other

Gap junctions in animals

Plasmodesmata in plants• Functionally similar to gap junctions• Allow passage of ions and molecules between

adjacent cells• Different in that they are open channels where

the cell membrane of one cell is continuous with adjacent cell membrane

• Desmotubule connects ER membrane of adjacent cells

Plasmodesmata in plants

Question 9

Cardiac cells contain ____which allow them to have direct signaling.

A) DesmosomesB) Gap junctionsC) Intermediate filamentsD) HemidesmosomesE) Tight junctions

Apoptosis

• Programmed cell death• Cell shrinks and forms rounder shape– Due to destruction of nucleus and cytoskeleton

• Plasma membrane forms blebs– Irregular extensions that break away

Kerr, Wyllie, and Currie found that hormone signals can initiate apoptosis

• ACTH known to increase number of adrenal cortex cells

• Prednisolone suppresses ACTH synthesis and decrease number of adrenal cortex cells

• Even in control samples, researchers observed apoptosis

• In prednisolone-treated rats, the rate was higher• Results indicate tissues decrease cell number and that

cell death was induced, in this case, by a hormone• Coined term apoptosis