Social cells Flashcards
(31 cards)
How do cells communicate?
In multicellular organisms, cell survival depends on cell-to-cel communication. Cell interact with each other by releasing EXTRACELLULAR MOLECULES influencing the behaviour of distant cells.
Cell growth, differentiation metabolism and death depend on cell-to-cell communication.
The key factors in cell-to-cell communication are the LIGANDS (the signalling molecules) and the RECEPTORS (the receiving molecules capable of translating the extracellular signal into an intracellular modification).
Ligands
Can be released in the EC space by:
- Exocytosis
- Diffusion
- Expressed on the cell surface
Depending on the distance they can travel before starting communicating with another cell/tissue.
SHORT DISTANCE COMMUNICATION
- Contact- dependent
- Autocrine signalling
- Paracrine signalling
LONG DISTANCE COMMUNICATION
- Synaptic
- Endocrine Signalling
Speed of Signalling
1) HORMONES
slow diffusion in the bloodstream
ENDROCRINE SIGNALLING
2) LOCAL MEDIATOR
PARACRINE SIGNALLING
3) NEUROTRANSMITTERS
100m/sec for the electrical impulse
SYNAPIC SIGNALLING
Endocrine signalling
- long-distance
- ligands are Hormones
- tend to be lipophilic
- very specific; only cell/organs presenting appropriate receptors will be influenced
- very potent - little variations on hormone concentration can have a big effect on the entire organism
- may be produced by a gland
Paracrine signalling
- Short-distance cell-to-cell communication, exact distance not quantified
- Vast range of different ligands that can start a paracrine signalling:
-> Growth factors
-> Gases
-> Inflammatory mediators - The concentration of the ligands is usually low and can be controlled in several ways:
-> enzymes
-> ECM
-> Antagonists
-> Inhibitors
Autocrine signalling
It’s the cell signalling to itself
It can decrease or promote the signalling initiated by the cell itself (NEGATIVE OR POSITIVE feedback)
Ligands promoting autocrine signalling include:
- Cytokines
- Growth factors
- Hormones
Juxtacrine/contact dependent signalling
Three forms:
1) Membrane proteins on each cell interact
2) Membrane proteins interact with part of an extracellular matrix
3) Junctions link cells allowing small molecules to pass between
Synaptic signalling
Technically short distance but allows RAPID LONG DISTANCE SIGNALLING.
Coordinate the behaviour of cells far apart from each other.
It is very specific; between neurons, between sensor and neuron or between neuron and effector cell.
How is the extracellular signal converted into an intracellular modification?
The vast majority of signalling molecules bind to receptors.
Ligand-receptor interaction promotes a CONFORMATIONAL CHANGE in the receptor. Most of the receptors are situated on the plasma membrane but some can be intracellular.
Some messengers can also bind ion channels or cause the synthesis of a second messenger.
The cells need to express the receptor for the messenger to pass on the message (competent cell).
Different cells contain different pools of receptors or different concentration of receptors.
One messenger can active different isoforms of the same receptor inducing different biological effects.
One receptor can also bind different ligands and with different affinity, again mediating different biological effects.
There can be an AMPLIFICATION OF THE SIGNAL within the cell and CROSS-TALK between different signalling cascades.
Receptors
Four main types:
1) ION-CHANNEL coupled receptors
2) G-PROTEIN coupled receptors transmission
3) ENZYME- coupled receptors (especially receptor tyrosine kinase)
4) NUCLEAR receptors
They work at different speed and/or for different lengths of times -> Different molecular structures.
Ion concentrations
outside cell:
- Potassium -> lower
- Sodium -> higher
- Chloride -> higher
- Calcium -> higher
inside cell:
- Potassium -> higher
- Sodium -> lower
- Chloride -> lower
- Calcium -> lower
Transport across the membrane:
PASSIVE TRASPORT
diffusion through bilayer and through protein channels
+ facilitated diffusion
Facilitated diffusion vs diffusion
- transport mechanism is specific
- limited capacity
- transport can be affected by competition
Transport across the membrane:
ACTIVE TRASPORT
Carrying substances against the concentration gradient.
2 mechanisms:
1) Primary active transport
2) Secondary active transport
Ion pumps
Cells have a continuous leakage of ions:
- uniporter
- symporter
- antiporter
Pumps can transport ions against their concentration gradient -> sodium (primary active transport).
1) Glucose (secondary active transport)
coupled to sodium uptake and co-transporter.
2) Calcium
cytosolic concentration needs to be kept low, use of ATP and sodium.
Ion channels
Proteins within the cell membrane.
Specific ions.
Types:
1) LIGAND-GATED ION CHANNELS
ions move through open channel -> change in electrical properties of cell.
2) VOLTAGE-GATED ION CHANNELS
Activation gate (closed but capable of opening)-> inactivation gate (closed and incapable of opening until return to resting state).
3) LEAK CHANNELS
4) STRETCH-ACTIVED CHANNELS
Importance of Ion Channels
- Muscle paralysis
- Heart disease
- Local anaesthetics
Cell membrane potential
is not the same as an action potential.
All cells have a resting membrane potential, regardless of whether they are able to propagate action potentials.
RMP= the potential across the membrane when there is no action potential being propagated.
Excitable vs. non-excitable cells.
Membrane potentials
- skeletal muscle = 90mV
- synovial fluid = 30
- cartilage = 15
- red blood cells = 20
- cardiac myocyte = 90
Cell signalling
Ability of cells to receive and act on signals fundamental to life. All physiological signals are mediated through proteins.
Proteins receiving signals are termed receptors.
Signals are converted to a cellular response, involving chemical processes - SIGNAL TRANSDUCTION.
Signal transduction is specific and very sensitive
- Specific:
precise binding between the signal molecule and the receptor - lock & key theory.
- Sensitive:
receptors detect concentrations of 10-6 - 10-9 molar.
Ligand-gated ion channels
- control fast synaptic events
- binds to the receptors -> conformational change allows transit of ions across the membrane
- binding and channel open in milliseconds
- no intermediate biochemical processes are involved in producing cellular effects.
G protein-coupled receptors
GPCRs associated with the signalling for wide range of processes.
Structure: 7 membrane-spanning alfa-helices -> coding for 800 GPCRs identified.
- Signals transducing molecules
- G proteins are comprised of 3 subunits -> inactive
G proteins exists as alfabetagamma trimer with GDP bound to the alfa subunit - G proteins are tethered to the cell membrane by the alfa and gamma subunits, but are freely diffusible in the plane of the membrane.
GPCR activation and inactivation
- Ligand binds to the GPCR at the ligand binding site
- Binding of ligand causes a conformational change
- This results in coupling with the trimeric G protein causing a conformational change in the G protein
- GDP on the alfa-subunit of the G protein dissociates and is replaced by intracellular GTP
- The alfa subunit-GTP complex and beta gamma-complex dissociate from the receptor and from each other and become free to diffuse in the membrane. The a subunit-GTP complex and the ßy-complex are free to interact with various enzymes or ion channels leading to signalling within the cell.
- GTP is hydrolysed to GDP by GTPase activity of the a-subunit.
- The resulting a subunit-GDP complex reunites with the By-complex and signalling stops.
Main classes of GPCR
There are 4 main classes of G protein, different alfa subunits show selectivity with respect to receptors and secondary messenger systems with which they interact:
- Ga s, and Ga i;
produce, respectively, stimulation and inhibition of adenylyl cyclase which converts ATP to cyclic AMP (cAMP) -> cAMP is a secondary messenger that activates kinase enzymes involved in energy metabolism, cell division and differentiation, ion transport, ion channels and contractile proteins in smooth muscle - Ga q
catalyses phospholipase C to produce inositol triphosphate (IP) and diacylglycerol (DAG)
-> IP is a secondary messenger which leads to the release of intracellular Ca2+ - important role in the action of many hormones - > DAG activates protein kinase C, which plays an important role in many different aspects of cell function
- Ga o
has a role in the function of K+ and Ca2+ channels and is the most abundant subtype in the brain
The primary effectors of Gßy complexes are ion channels, adenylyl cyclase, phospholipase C and Pl3 kinase.
