Cell communication

How do cells generally communicate with each other?

Via receptors that bind to ligands (signalling molecules)

General outcome of cell signalling

rapid changes in protein function and/or slower changes in gene expression

What type of ligands can cross membranes to activate intracellular receptors

Lipophilic (Hydrophobic)

How do hydrophillic ligands work

bind to cell surface transmembrane proteins

Signal transduction receptors require the activation or generation of what

second messengers

What do second messengers do

transmit the signals from the cell surface

3 basics modes of signalling

ion channels, enzyme coupled receptors, G protein coupled receptors

How do lipophilic ligands work and what are they

They are nonpolar molecules, they can diffuse across the membrane and binds to the receptor in the cell

How do hydrophilic ligands difuse across the membrane

cell surface receptors bind to it on the outside and carries info to change proteins function

3 steps of cell communciation

1. (reception) Binding of some molecule which was released from a cell. 2. (transduction) Signal transmitted from surface (from relay molecules). 3. (response) A physiological change

How do signalling molecules act

can act over long or short differences

Where do signalling molecules come from

they are secreted,

How are secreted signal molecules made

Cell in question pumps signal molecule out and moves away to interact with receptor

3 signal methods

Paracrine, endocrine, synaptic

How does paracrine signaling work

cell secrets molecule to act locally on neighboring cells (local mediators), signalling molecule that was secreted diffuses only short distance away(cell must be near)

How does endocrine signalling work

signalling molecule travels through bloodstream in order to interact with molecules far away

How does synaptic signaling work?

signalling molecule travels across axon, a specific cell is chosen

How does autocrine signaling work?

cell can receive a signal that it can produce, sends signal to SAME CELL

How can autocrine signalling be used in embryonic development

Through positive feedback. Once a cell has commited to a pathway it can secrete autocrine signals to itself to reinforce its state

How (2 ways) do signalling molecules work (action mechanism)

1.They send signals that alter a protein already in the cell (enzymes on/off, protein to move) (rapid change). 2. Send signals to alter protein synthesis (turning on/off genes) (slow change)

How do they combination of signals influence a signalling molecule

A cell is exposed to hundreds of signals in its environment, so a cell may be programmed to respond to one combination to initiate growth and another for division (the cell must recieve all signals from the combination)

Different combinations of signals in a cells enviroment have different what on cells

different actions, some signals for growth/divison, differention, or perfrom a function

Most cells are programmed to depend on _________ _______ of ______ to survive

specific combinations of signals

Because different cells depend on different signals cells will only survive if?

they remain in their specific environment

different cells have different receptors for what kinds of signals

different signals

A cells response to a signalling molecules varies according to

the unique collection receptor proteins the cell posses

How can 2 cells have a different response to the same signals

Because they each have their own unique receptors and/or the intracellular signalling machinary which the cell interprets what it recieves

How can the same signalling molecule have different effects on the same cell types

depending on its concentration, cells adopt differents fates depending on their position in the concentration gradient

Cells are specialized to recieve and respond to a wide varity of?

stimuli

Types of signals (stimuli)

mechanical, light, heat, and chemical

Chemical stimuli comes in many different forms: name some

AAs, small peptides, proteins, nucleotides, steroids, fatty acid derivatives, and dissolved gases.

Most chemical stimuli/signals are secreted from what

from the signalling cell into the extracellular space through exocytosis

Some chemical stimuli/signals that arent secreted through exocytosis are exposed to the extracellular space how

they remain tightly bound to the signalling cells surface (contact dependent) and released by diffsusion through plasma membrane

Many signalling molecules are _____ soluble

lipid soluble

How do lipid soluble lipids move across the plasma membrane

they can easily difuse across the PM and interact with receptors inside the cell

Steroid hormones vary in what and are all synthesized by what

in chemical structure all synthesized by cholesterol

Steroid hormones all bind to what type of receptors

intracellular

All steroid hormones require what to get to the receptor

carrier proteins

Intracellular receptors for steroid hormones are members of what family

the nuclear receptor family

Prior to binding intracellular receptors are bound to what and are what

bound to inhibitory proteins and are inactive

How are inhibitory proteins disassociated from intracellular receptors

When the ligand binds it causes a conformational change which causes the inhibitory protein to dissassociate

When inhibitory proteins dissocaite from intracellular receptors what is exposed

exposes a site which binds to the promoter region upstream of a specific gene

When the exposed site of an intracellular receptor binds to the promoter region upstream of a specific targeted gene what happens to the targeted gene

transciption of that gene is increased, producing specific proteins that changes a cells behavior

Intracellular receptors dont need what

a signal transduction pathway

What type of activation does intracellular receptors work through

direct activation can act more quickly

The majority of chemical stimuli are?

small, polar, water soluble molecules

3 Major types of receptors

ligand gated ion channels, enzyme coupled receptors, and G protein coupled receptors

Openning and closing of ion channels are regulated by what

ligand binding

ion channel coupled receptors are involved with what

in synaptic signalling between neurons and other excitable cells (ion concentration determines whats going on)

When do Ion channel receptors open

when signalling molecules binds to receptor allowing ion flow in our out

Ion channels opened or closed by what

small number of neurotransmitters

After an ion is permeable what occurs

potential membrane changes

G protein coupled receptors are a large family of what

multipass transmembrane proteins

G-protein coupled receptors indirectly regulate what

the activity of a nearby target protein that is located in the membrane

G protein coupled receptors contain a GTP binding complex thats acts as what

acts as a middle man between an activated receptor and its target

Procces of G protein activating the enzyme

Signal molecules binds to inactive receptor, binds to inactive proteins, now active G protein can activate the enzyme

Enzyme coupled receptors are usually what

usually kinases

simple Structure of enzyme coupled receptors

single pass transmembrane proteins

How do enzyme coupled receptors function

directly as protein kinases or associate directly with and activate other protein kinases

Protein coupled receptors indirectly regulate what

the activity of a nearby target protein (enzyme or channel) that is located in the membrane or cytosol often via kinase

Binding of ligand to enzyme coupled receptor causes receptor molecules to do what

Cluster

What does clustering allow

allows kinase domain to activate kinases, leading to full activate so they can phosphorylate downstream targets

3 steps of how intracellular signalling molecules work

1.. Cell surface receptors carry the signal (1st messenger) across plasma membrane 2. A combination of activated enzymes and small intracellular molecules called second messengers (must be generated from something) amplifies the signal and spread it throughout the cell. 3. Activated effector proteins regulate cells response

What do secondary messengers allow in terms of diffusion

allows diffusable signal

Many intracellular signalling proteins function as _______ that are activated by ________/_________ and ______/______

molecular switches, kinases/phosphates (through phosphorlation/dephosphorylation), or GTPases/GTP binding proteins (GAPS/GEFS activate/deactivate)

How are signalling complexes assembled

usually preassembled or binding of ligand to receptor activates it

Signalling complexes are usually organzined into what

higher order complexes

How are signalling complexes activated

enzymes activated by a receptor protein

Advantages of signalling complexes

increase speed, efficency, and specificity of a cellular resonse

How and why can signalling complexes increase speed, efficency, and specificity of a cellular response

How:speed-can move kinase close, specificity-can allow kinase to choose specific target Why: dont need to move targets, allow target (specific to be choosen)

2 ways signalling complexes can be formed

1. organized around a scaffold protein 2. Assembled following receptor activation.

Process of signalling complexes being organized aorund a scaffold protein

when receptor binds to ligand it recruits binding proteins or scaffold proteins already bound and binding to receptors turns on other proteins that can be phosphorlayted

Process of signalling complexes being assembled follwing receptor activation

the receptor acts as scaffold and the cytoplasmic tail can be phosphorylated which allow binding proteins to bind and can then be phosphorylated

Process of signalling complexes being assembled on phosphortylated phosphoinstide lipids

uses surface/inner membrane giving 2d organization by altering polar head group of lipids, proteins bind inside and inositate can be phosphorylated

receptor tyrosine kinases are activated by what

by clustering

tyrosine kinases do what upon ligand binding

dimerize and phosphorylate themselves

Proccess of tyrosine kinase reacting to SM

1. Dimerize and phosphorylate themselves when ligand binds 2. the now phosphorylated tyrosine becomes binding site for other signal molecules 3. Proteins specialized to bind phosphorylated tyrosine then bind 4. Another SM such as RA binds to target protein when bound to GTP 5. RASs then initiate a cascade of phosphorylation events mediated by MAP kinases (group)

Can different SMs actiavate the same pathway

yes

Can signalling pathways have convergent pathways and also different ones

yes

General mechansim of G coupled protein recpetor responding to SM

The trimeric G-protein where alpha subunit binds GDP and when ligand binds it acts as GEFS switching GDP for GTP which activates protein causing dissociation from beta and gamma chains

What do trimeric G proteins do when the alpha subunit is bound to GTP?

They interact with the enzyme adenylyl cyclase.

What does adenylyl cyclase convert ATP into?

cAMP (cyclic adenosine monophosphate).

What does cAMP bind to in order to cause a conformational change?

PKA (protein kinase A).

What happens when PKA undergoes a conformational change?

The catalytic subunit is released and becomes active PKA.

Where does active PKA move to after activation?

Into the nucleus.

What does active PKA phosphorylate in the nucleus?

A gene regulatory protein called CREB.

What does CREB bind to on DNA?

Cyclic AMP response element (CRE).

What protein binds to CREB to alter chromatin structure?

CBP (CREB-binding protein).

mech 1 of GPCR responding to SM

Trimeric G proteins, when alpha subunit bound to GTP interacts with enzyme (adnelyl cyclase) converts ATP into cAMP (secondary messenger), cAMP then binds to PKA causing conformational change that releases catalytic subunit which can then be active PKA, the active PKA moves into nucleus where it phosphorylates a gene reg protein (CREB) and binds to cyclic AMP response element on DNA and CBP binds to CREB and alters chromatin structure

What G protein is used by GPCR when responding to a signaling molecule?

Gq

What happens when the alphaq subunit of Gq binds to GTP?

It binds to phospholipase C.

What does phospholipase C cleave?

Phosphoinositide head group.

What is produced when phospholipase C cleaves phosphoinositide?

IP3

What is the role of IP3 in the cell?

It is soluble and can diffuse into the ER.

What receptor does IP3 bind to in the ER?

IP3 receptor

What happens when the IP3 receptor in the ER is activated?

Calcium flows out of the ER into the cytoplasm.

What occurs as a result of calcium release into the cytoplasm?

Another cell channel opens, allowing calcium to flood into the cell.

What protein can be activated by calcium in the cell?

PKC

PKC activated by what

calcium

IP3 does what

releases caclcium from ER