Signalling between cells Flashcards
Why do cells communicate?
- Process info
- Sensory stimuli
- Self preservation
- Survival
- Voluntary movement
- Homeostasis
- Thermoregulation
- Glucose homeostasis
What are the different types of signaling?
- Endocrine signaling: hormone travels via blood and acts on distant target
○ E.g insulin alpha cells, adrenalin - Paracrine: hormone acts on cell adjacent to it
○ e.g hyperglycemia insulin secreted by beta
cells inhibits glucagon secretion
○ No2 produced by endothelial cells in blood
vessels
○ Osteoclast activating factors produced by
adjacent osteoblasts - Autocrine signaling: signaling molecule acts on same cell
○ Activated T lymphocyte initiates cascade
within self because has IL2 receptor on
surface secreting IL2
○ IL2 binds on own receptor so this effect
○ Acetyl choline
○ Growth factors from tumor cells - Membrane-attached proteins
- Interaction between membrane proteins from
two different cells
- T-cell receptor interacting with MHC class II
molecule
What are the types of receptors that signal can interact with?
- Ionotropic: ligand binding opens ion permeable pore
- G protein coupled: ligand binding leads to receptor clustering which activates intracelllular G protein
- Enzyme linked receptor: ligand binding leads to receptor clustering which leads to clustering and activates internal enzymes
- Intracellular: membrane permeable ligands binds to receptor inside cell (inside of cell)
What type of receptor are nicotine acetylcholine receptors?
Ionotropic
Where are they found?
- on skeletal muscle at neuromuscular junction begins depolarization leading to muscle contraction
- Also found in brain (important in addiction)
How are signals transduced?
- Ligand binds to receptor
- Change in conformation opens pore
- Pore allows ions to move in and out of cell according to concentration gradient
- Primarily Na, secondarily Ca
What is another type of ionotropic receptor?
GABA: located in many CNS neurons
Acts once ells which cause dampening of function
What is the structure of G protein coupled receptor?
- 7 transmembrane regions
- In resting state not associated to heterotrimer
- Heterotrimer with alpha, beta, gamma subunits
- GDP not part of heterotrimer
- Beta and gamma subunits always bound to one another
How are signals transduced in GpcR?
- Ligand binds and change in receptor conformation
- Ligand binding causes the G protein complex to associate with the receptor resulting causing GDP exchange for GTP
- GTP provides energy for alpha and beta-gamma to dissociate
- Once alpha subunit attached to target protein, internal GTPse activity in subunit causes GTP molecule to change to GDP
- Alpha subunit unbinds from target protein and reforms heterotrimer with GDP
- Ligand bound to receptors all the time
- GDHT can be activated as long as ligand bound
What are the types of G-alpha subunit?
GsPLR: s for stimulatory of adenylate cyclase
- E.g beta 1 adrenergic receptors - Noradrenaline binds - Converts ATP--->cAMP - cAMP increases PKA levels - Increases heart rate
GiPLR: i inhibitory so has opposite effect
- E.g M2-muscarinic receptor - Inhibits adneylyl cyclase - Reduces PKA - Decreases heart rate
GqPLR: AT-1 angiotensin receptor
- activates phospholipase (PLC) - converts P1P2-->IP3 + DAG - IP3 increases intracellular calcium - DAG activated PKC - vasoconstriction
How do enzyme linked receptors work?
- Ligand binding results in receptors clustering
- Receptor clustering activates enzyme activity within the cytoplasmic domain
- The enzymes phosphorylate the receptor
- This phosphorylation leads to the binding of signalling proteins to the cytoplasmic domain
- These signalling proteins recruit other signalling proteins and a signal is generated within the cell
- The signal is terminated when a phosphatase dephosphorylates the receptor
What are the functions of enzyme linked receptors?
- recruit other signalizing proteins and signal generated within cell
What are examples of tyrosine kinase linked receptors?
- Ligand: Insulin
Receptor: CD220 - Ligand: epidermal growth factors, transforming growth factor beta
Effect: cell growth, proliferation
What are other types of enzyme linked receptors?
- Glanylyl-cyclase linked receptor
2. Ser/Thr kinase linked receptor
What are the types of intracellular receptors?
Type 1: in cytoplasmic compartment
- attached to heat shock proteins (chaperone molecules)
- Hormone binds to receptor (need to be membrane permeable)
- Bind to receptors which dissociates from heat shock proteins
- Form homodimer
- Homodimer moves into nucleus
- binds to DNA causing inc/dec transcription (effect takes longer)
Type 2: located in nucleus, already bound to DNA
- Ligand comes in, moves through nuclear envelope and binds to receptor on DNA causing transcription change
What is an example?
- Type 1: glucocorticoid receptors
○ Ligand: cortisol
○ Agonist: glucocorticoid
○ Physical effect: downregulate immune
response, gluconeogenesis - Type 2: thyroid
○ Ligand: thyroxine (T4) and triodothyronine (T3)
○ Agonist: thyroid hormones
○ Physical effect: growth and development
What do intracellular receptors regulate
Physiological processes regulated by intracellular receptors include immunosuppression and physical development.
