Receptor Physiology And Signalling Flashcards
Changes in a cell’s membrane potential (seen in gap junction between cells where ions are passing through protein connection between cells)
Electrical signal
Molecules secreted by cells into extracellular fluid; responsible for the majority of activities within the body (seen in secretion of a neurotransmitter that binds to a receptor protein)?
Chemical signals
Characteristic of Signalling Pathways
Multiple, hierarchical steps
Amplification of the hormone-receptor binding event, magnifying the response
Activation of multiple pathways and regulation of multiple cellular functions
Antagonism and regulatory control
Relay of a message from the sender cell to a receiver cell to initiate a cascade of events
Transduction
Signal molecule that binds to a receptor
First messenger: brings info to target cells
Ligand
Response of cells
Altered ion transport Altered metabolism Altered gene expression Altered cell shape or movement Altered cell growth and division
Secondary messengers and serve as the amplification steps
Intracellular signalling proteins
Local Cell Communication
important during development and in immune responses
Contact-dependent signals
Membrane-associated ligands
Communication Junctions (Direct interactions) gap, adhering, tight
Chemical signals
autocrine, paracrine
Ligands on the cell membrane of one cell bind to the receptors on the cell membrane or target cell
Provide spatial clues in migrating cell
Contact-dependent signals
Membrane-associated ligands
Link direct cytoplasm of two adjacent cells
Fastest way of cell-to-cell communication
Allows exchange of ions, secondary messengers and metabolites
Allows cells to be electronically coupled which is important for activity of CARDIAC and SMOOTH MUSCLE cells
Made up of proteins which can be opened or closed called
Gap junctions
Connexins
Have transmembrane proteins that link with the adjacent cell through the actin filaments in cytoskeleton
Maintenance of normal cell structure
Serve as a signalling role during organ development and remodelling
Cadherin
Adhering junctions
Consists of a network of proteins
Limit the passage of cell molecules and ions through the space between the cell
Claudins
Tight junctions
Diffuses molecukes through ECF to act on nearby cell
Chemical signals
Autocrine - sender and receiving cell is same cell; development where cells reinforce their identities
Paracrine - released by one type of cell and diffused to receptors of adjacent cells or cells in proximity via ECF; does not get into the blood
ex. Fibroblast growth factor FGF
Long distance communication
Synaptic transmission
Endocrine
Neuroendocrine
Binds to extracellular domains
SLOW response
Peptided, Amino acids
Polar Lipophobic ligands
Diffuse through phospholipid bilayer
RAPID response due to AMPLIFICATION STEP
Steroid, thyroid hormone, Vit A and D
Nonpolar ligands Lipophilic
Ionotropic receptors
Conformational change happens to the channels when the ligand binds with the receptor -> opening of the channels to allow the passage of ions
The ligand that binds to the cell changes the cell’s polarization and activates the ion channels directly and rapidly
Ex. Acetylcholine
Ligand-gated ion channel
7 transmembrane domain receptors
Serpentine receptors
An integral protein that crosses the cellular membrane 7 times
Physiologic response is mediated by G proteins of GTP binding protein family
G-protein Receptors
In the absence of the ligand, G proteins are inactive and form a heterotromeric complex (GDP+ alpha subunit)
Upon ligand binding to the inactive GPCR, conformational change in the G protein that promotes the release of GDP now (GTP +alpha subunit)
GDP-GTP exchange stimulated dissociation of the complex from the receptor, disassembly of trimer into free alpha subunit and beta,gamma complex
GTP-bound alpha subunit now interact in the plane of membrane with downstream effectors such as adenylate cyclase and phospholipase
Beta, gamma subunit can now activate ion channels or other effectors
GPCR Mechanism
Hydrolysis of GTP to GDP and inorganic phosphate by GTPase INACTIVATES the signalling events of alpha subunit -> inactive alpha-GDP complex that dissociates from its downstream effector and reassociate with beta, gamma subunit
GTPase activity is enhanced by Regulation of G Protein Signalling family of proteins as long as ligand is attached, it will continue to activate G protein
GPCR Mechanism
G PROTEIN Signalling Pathways
Adenylyl cyclase Phosphodiesterase Phospholipase Ca - directly stimulated through Gs Protein phosphatase B gamma Monomeric G protein - GTP binding protein
Alpha subunit binds to this
Converts ATP into cAMP
cAMP then open ion channels or activate PKA (Protein Kinase A) which regulates the effector protein activity
ai inhibitory, adenylate cyclase not activated
ex: L type calcium channel
Adenylate cyclase
Found in cytoplasm and helps in muscle contraction
Activated by cAMP to open Ca channels
Calmodulin
Used in phototransduction or light perception
Ligand = light or proton
Activated by Gi (G protein with alpha subunit)
Light interacts with the receptor coupled to at (transducin)
Activates phosphodiesterase
Breaks down cAMP back into GMP
Leads to the closure of cGMP - dependent channels
Phosphodiesterase
Acts on phospholipids in plasma membrane
Products:
DAG - activates Protein Kinase C
IP3 - promotes increase of Ca in the cell
Phospholipase
Cuts bond at carbon 1
Results to free fatty acid and DAG
Phospholipase A1
Cuts at carbon 2
Activated by Gi or Go
Results to arachidonic acid and stay within the cell or be converted to eicosanoids
Phospholipase A2
Cuts at carbon 3
Activated by Gq
Results to hydrolysis of Phosphatidylinositol 4,5 diphosphate into Inositol Triphosphate (IP3) and DAG
Phospholipase C
Cuts phosphodiester bond
Results to free headgroup and Phosphatic acid
Phospholipase D
Reverses action of kinases
Dephosphorylates the proteins phosphorylated by PKA
Protein phosphatase
Actin cytoskeleton, cell cycle progression, gene expression
Rho
Transport of RNA and Proteins
Ran
Gene expression, cell growth, associated with oncogenes
Ras
Glucagon
B adrenergics
Effector
Inc adenylyl cyclase
Gluconeogenesis, lipolysis, glycogenolysis
Odorant
Inc adenyly cyclase
Acetylcholine
Alpha 2 adrenergics
Decrease adenyly cyclase
Inc Potassium channels
Slowed heart rate
M2 cholinergics
Dec Ca channels
Secondary messengers
cAMP AND cGMP IP3 and DAG Ca Arachidonic acid and metabolites HETE ETE
Function directly as enzymes when activated or are closely associated with the enzymes they activate
Catalytic Enzyme Coupled Receptors
Ligand binds to receptor
Receptor directly converts GTP to cGMP
Receptors that mediate cellular responses to ANP and NO
Recetor Guanylyl Cyclase
Intracelljlar domain is a serine/threonine kinase that phosphorylates proteins containing serine/threonine amino acids
Like TGFB fibrosis
Receptor Serine/Threonine Kinase
Phosphorylates tyrosine residues on themselves to become fully active to allow the phosphorylation of other proteins
Ex. EGF, PDGF
Insulin, Mitogenesis, Protein synthesis, Glycogen synthesis, Glucose transport
Receptor Tyrosine Kinase
the JAK is the catalytic part instead of receptor itself
Cytokine receptors consist of at least 2 chains: Janus kinase and cytoplasmic domains
One phosphorylates the other dephosphorylates is found on cytoplasmic areas
Tyrosine-Kinase Associated Receptors TKAR
Receptors located in cytoplasm and in the nucleus
Bind to specific DNA sequences hormone response elements in regulatory region of responsive genes
Steroid hormone, thyroid hormone, aldosterone
Intracellular Nuclear Receptors
