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Chapter 9A: GPCR Signaling - Coggle Diagram
Chapter 9A: GPCR Signaling
Why do cells send and receive signals?
Communication between cells in multicellular organisms, to regulate:
Responses to the environment: thrive long enough to reproduce
Homeostasis: Maintain and replenish functions for decades
Development: generate patterns of the "right" cells in the "right" places so that they function as an organism
Basic principle of cell communication
one cell emits a chemical signal through SIGNALING MOLECULES
--> signaling molecule binds to RECEPTOR
--> a cell receives the signal and responds
How do cells send and receive signals? distance; ligands and receptors
Signaling molecules are LIGANDS
They come in many different forms
gases: nitric oxide in mammals, ethylene in plants
small molecules: adrenaline (polar), steroids (non-polar)
peptides: growth factors, insulin, cytokines
Signaling molecules can be passed directly from cell to cell
In plants: through plasmodesmata (connects cytoplasm and the ER between cells)
plasmodesmata enables transmission of proteins, RNA, and small molecules across a tissue (cell wall is impermeable for molecular transport)
In some animal tissues: through gap junctions (connects cytosol of one cell and another)
gap junctions enable RAPID transmission of ions and small molecules as signaling molecules across a tissue
example: in neurons
Dopamine
when gap junctions are opened
when gap junctions are closed: DA goes throughout the cell but CAN'T go to surrounding cells because connections are closed
important in cell coordination (ex. muscle contraction in heart, coordination of neurons)
"Contact dependent signaling": by cell component touching receptor on another cell right next to it (transmembrane protein connects them)
neighbors receive instructions from neighbors (bidirectional signaling)
ex. a sheet of precursor turns into a sheet of neurons interspersed between helper cells
2 neuronal precursors start out the same
when Delta (signaling molecule) and Notch (receptor) touch between the two neuronal precursor cell -->
one cell activates delta (becomes a neuron)
the other cell activates notch/inactivates delta (becomes a helper cell)
Or signaling molecules can be released from one cell and diffuse SHORT distances to another cell (PARACRINE SIGNALING)
important early in development
important in signaling within organs
Or signaling molecules can be released into the BLOOD SYSTEM to be transported LONG distances across body (ENDOCRINE SIGNALING)
coordinate MULTIPLE organs (insulin)
regulate WHOLE BODY changes (estrogen and testoserone in puberty)
Receptors
cell surface receptor: transmembrane protein, binds polar signaling molecule
intracellular receptor: INSIDE the cell, binds small, nonpolar signaling molecules
What does cell signaling do? Quorum sensing and fight or flight response
In bacteria (single cells): quorum sensing
When there are HIGH concentrations of similar bacteria nearby, the bacteria becomes PERMEABLE TO DNA (induces DNA uptake)
Bacteria secretes a peptide
peptide activates a receptor IF concentration is high enough
low cell density (low bacteria density) means low peptide concentration
receptors are NOT activated
In animals: fight or flight response
symptoms: rapid breathing, increased heart rate, breakdown of glycogen and release of glucose into bloodstream in the LIVER
fight or flight response associated with hormone adrenaline binding to beta-adrenergic receptors (GPCR)
adrenaline binds to beta-adrenergic receptors in heart
ion channels open
increased rate and intensity of muscle contraction
adrenaline binds to beta-adrenergic receptors in liver
breakdown of glycogen and transport of glucose into bloodstream
beta-adrenergic receptor is a GPCR (shaped like a 7 helix basket)
binding site: outside of cell
transmission: binding of ligand induces a conformational change inside cell
Intracellular Signaling: what happens when GPCR is activated?
key steps of cell signaling cascade inside recipient cell
receptor activation
signal transduction
response
termination
Signal transduction
START: adrenaline is released into bloodstream
adrenaline binds to beta-adrenergic receptor (ACTIVATION OF GPCR)
Galpha binds to GTP/Ga and Gbeta/Ggamma subunits separate (activation of heterotrimeric G protein)
Ga/GTP binds to and activates adenylyl cyclase
adenylyl cyclase produces cAMP
cAMP activates PKA
PKA phosphorylates proteins
1 more item...
INACTIVE: When GDP is bound to G-protein
ACTIVE: When GTP replaces GDP and binds to a, B/Y subunit separates
INACTIVE: GTP Hydrolysis (a phosphate comes out) --> GDP and inactivation of Ga protein
Primary function of cAMP: activation of PKA
binds to inactive PKA (has catalytic and regulartory subunits)
binds to regulatory subunits --> releases activated catalytic subunits (PKA is activated)