BIOLOGY 1A Lecture Notes - Lecture 27: Robert Lefkowitz, Signal Transduction, Sensory Neuron
Cell communication involves signaling molecules (ligands) and receptors
Ligand: signaling molecule
○
Receptor protein: binds to signaling molecule
○
Signal transduction: pathway converting signal into response
Reception
1.
Transduction
2.
Response
3.
○
•
Signaling:
Endocrine:
Long distance; hormones
§
○
Paracrine:
Medium distance; Signaling cell signals target cells
§
○
Synaptic:
Sensory; neurotransmitters
§
○
Contact dependent:
Short distance; membrane bound signal molecule
§
○
•
Theme 1 in signal transduction: GTP binding proteins or G-proteins
Switch proteins on and off
○
GTP binds- protein turns on
○
GTP is hydrolyzed then GDP is attaches and makes protein inactive
○
When a GDP falls out, a GTP comes in because there is a lot more GTP
around than GDP
○
•
GPCR's are the largest of receptor proteins in animals
Common target of pharmaceuticals
○
Involved in sensory systems- taste, smell,
○
•
Discovery and study of GCPR: Robert Lefkowitz and Brian Kobiika
•
Purification of the beta-adrenergic receptor
Figure out what the receptor that binds adrenaline is?
○
Treat the lipids with a detergent, the receptor goes into the detergent
○
Take the membranes and pass them over a column with beads
○
The beads have the ligand (adrenaline) bound to them
○
All the proteins that are not the receptor will fall through, the receptor
will stick
○
•
GCPRs contain 7 transmembrane domains
Alpha helical domains
○
Signaling molecule binds to outside
○
•
GPCRs signal through G-proteins
Inactive state: No ligand in receptor
GDP attached to G-protein--> inactive
§
1.
Ligand binding exchange & activation: the signaling molecule attaches to
the activated receptor. GTP comes in and allows G protein to bind to the
receptor which is now activated
2.
Transduction and Response- the G-protein binds to the enzyme which is
not activated inducing a cellular response
3.
Hydrolysis and Inactivation: GTP is hydrolyzed into GDP, releasing a
phosphate and detaching from the enzyme making it inactive
4.
•
Many taste receptors are GCPRs
Bitter taste: T2R
○
•
Mutations in a gene encoding which of the following proteins might lead to an
increased taste sensitivity to bitter compounds but not other taste molecules?
The bitter compound taste receptor GCPR
○
•
Mutations in TAS2R38 may lead to differences in bitter taste•
The gustatory system
Each sensory receptor cell expresses a different taste receptor
Sweet, Salty, Sour, Bitter, Umami
§
Sweet, Bitter, Umami are GPCR
§
○
•
Signal transduction during bitter taste•
General signal transduction via GCPR, G-protein and phospholipase C•
Lecture 27 4/2
Thursday, April 5, 2018
9:09 PM
Document Summary
Cell communication involves signaling molecules (ligands) and receptors. Theme 1 in signal transduction: gtp binding proteins or g-proteins. Gtp is hydrolyzed then gdp is attaches and makes protein inactive. When a gdp falls out, a gtp comes in because there is a lot more gtp around than gdp. Gpcr"s are the largest of receptor proteins in animals. Discovery and study of gcpr: robert lefkowitz and brian kobiika. Treat the lipids with a detergent, the receptor goes into the detergent. Take the membranes and pass them over a column with beads. The beads have the ligand (adrenaline) bound to them. All the proteins that are not the receptor will fall through, the receptor. All the proteins that are not the receptor will fall through, the receptor will stick. Ligand binding exchange & activation: the signaling molecule attaches to the activated receptor. Gtp comes in and allows g protein to bind to the receptor which is now activated.
