Cell communication and signalling Flashcards
Importance of
Cell communication
- To sense and respond quickly to the environment
- Governs basic cell function response to external change bacterial cell plant bend fight or flight sweat shivering
- To quickly identify invading organisms and respond to them
Three types of junction
- Gap junction
- Anchoring junction
- Tight junction
Gap Junction
- 2 cylindrical channel (6 connexin proteins) adjacent cells joined to form a pore
- Allow bidirectional change between 2 cells no effect on EMC adhesion
- Only gap junction provide direct communication allows small intracellular water soluble during inorganic ions pass form cell to cell
Contact dependant
- Signalling molecule binds to receptor on interacting cell
- Exchange via gap junction
Endoctrine
- Signal hormone to travel through blood stream at distant body site insulin beta cells promote absorption liver and skeletal muscle
Paracrine
- Signals local release into extracellular local
Nitric oxide relax smooth muscle
Synaptic
- Specific signal at specialised junction
- Neural along nerve terminal release neurotransmitters receptor on target cells
Autocrine
- Signalling secrete extracellular signal bind to receptor on same cell
- Self-regulate stimulate own survival
Signal receptor
External surface imbedded to plasma membrane specific interaction
Signal transduction
- Signal receptor binding
- Convert and amplify the extracellular signal into different intracellular event
- Specific cell response
Signal receptor interaction
- Receptors are specific ligands complementary to mediate response
- Activated only by one type of signal cells
- Possess a receptor for the signal
- hydrophobic intracellular
- hydrophillic extracellular
Intracellular receptor
- Receptor proteins are intracellular in cytosol
- Hydrophobic signal molecule cross membrane to activate
- Hormone receptor complex act as transcription factor binding DNA sequence to modify transcription produce effector proteins
Membrane receptors
- Ion channel coupled
- G protein receptor
- Enzyme coupled receptor
- Signal receptor - always causes conformational change
Ion channel coupled
- Receptor conformational change after binding the signal activates the ion channel specific ion
- Chemical to electric
e.g. nerve cells and other electrical excitable cell such as muscle
Intracellular receptors
- In cytosol or nucleus of target cell
- Hydrophobic signalling molecules such a steroids and thyroid molecules
- Transcription factor binding DNA sequence to initiate transcription of specific genes to produce effector proteins
G protein coupled receptors (GCPRs)
- Transmembrane receptors
- G protein
Trans-membrane receptor
- Protein that crosses 7 times in the plasma membrane (fold)
- Ligand binding site is on the extracellular
side
G protien (switch on/off)
- On cytosolic side of the plasma membrane
- 3 subunits- α, β, γ
- α associated with inactive GDP
- ## Ligand binding activates GDP into GTP
Activation of GPCR’s
1) Signalling binds to receptor which undergoes conformational change
2) This change attracts and activates a G-protein and
its α subunit exchanges its GDP for GTP
3) This dissociates the α subunit and βγ complex
GPCRs effect and inactivation
- Both α subunit and βγ complex can interact and activate ion channels
- Activate membrane bound enzyme that are indolved in signalling transduction
GCPRs inactivation
- Activation of target protein by α subunit
- Hydrolysis of GTP by α subunit inactivates the subunit causing diassociation from target protein
- Inactivated α subunit reassembles with βγ to reform the inactive G protein
Enzyme coupled receptors
- Receptor cytoplasmic part either acts like the enzyme itself receptor tyrosine kinases (RTKs) or the receptor forms a complex with the enzyme
RTKs
- Membrane receptors that attach phospates to tyrosine amino acids
- Can trigger multiple signal transduction pathways at once, stimulating cell growth and cell survival
- Abmormal function can cause cancers
Enzyme coupled receptors
1) Ligand binding induces the pairing of 2 receptors (dimerisation)
2) Intracellular receptor parts (kinases) phosphorylate each other’s specific tyrosines
3) Phosphorylated tyrosine recruit many different intracellular signalling proteins
4) Some become phosphorylated and activated (signal transduction), a process required to trigger a complex response such as cell proliferation or differentiation
Transduction step
- Multisteps to amplify a signal
- Multistep pathways provide more opportunities for coordination and regulation
- Different transduction strategies (phosphorylation cascade or second messengers)
for different pathways
Protein phosphorylation cascade
- This phosphorylation (by kinases) and dephosphorylation (by phosphatases)
system acts as a molecular switch, turning activities on and off
Second messenger model
- readily spreads through body and amplifies signal
- small water soluable ions
- cAMP, cGMP, lipids and NO
- initiated by G protiens
Second messenger model in GPCR’s
- Activation of some G-protein-linked receptors can
activate a membrane-bound enzyme called adenylyl
cyclase that converts ATP to cAMP - cAMP exerts most of its effects by activating the
enzyme cyclic-AMP-dependent protein kinase (PKA) - Activated PKA catalyses the phosphorylation of
particular serines/threonines on specific target
proteins (e.g. involved in the glycogen breakdown)
With IP3
Second messenger model in GPCR’s
- Phospholipase C splits when activated into 2 small molecules inositol trisphosphate (IP3) and diacylglycerol
- IP3, opens Ca2+ channels in the
endoplasmic reticulum to release Ca2+ into the cytosol - Ca2+ signal activates some proteins
triggering many biological processes
Cell-receptor interaction
- Regulation of gene expression, turning transcription of specific genes on or off
