dag ip3 Молекулярные и клеточные механизмы обоняния · organ...
TRANSCRIPT
Olfaction — a mode of communication between animals
Recognition
stress signals (predator, aggression, fear)food identification territorial boundaries
Reproductive behavior
mate selectioncourtshipsexual behavior, maternal behaviorkin recognition
Septal organ
Glueneberg ganglion
Vomeronasal organ
Main
olfactory
epithelium
Main
olfactory
bulb
Accessory
olfactory
bulb
BV
basal
apical
ethyl octanoate4-heptanolide
Minty
Beta-cyclocitral
p-anisaldegyde 2,6-dimethylpyrazine
Fruity Nutty
Odorant space
General odorants are small hydrophobic molecules
volatile at ambient temperature
CH3-CH2-CH2-CH2-CH2-CH2-C-OCH3||
O
CH3-CH2-CH2-CH2-CH2-CH2-C-H||
O
CH3-CH2-CH2-CH2-CH2-CH2-C-CH3||
O
CH3-CH2-CH2-CH2-CH2-CH2-C-OH||
O
1-heptanol - citrus, sweet
1-heptanal - oily, unplesunt
Methyl heptanoate – pineapple, sweet
2-octanone – sweet, non-citrus
1-heptanoic acid – paint, chemical
Functional group theory
CH3-CH2-CH2-CH2-CH2-CH2-C-OH|
|
H
H
(4S,7R)-(-)-galaxolide
powerful musk odor(4R,7S)-(+)-galaxolide
almost odorless
(3R)-(+)-Fixolide
light, sweet, aromatic
(3S)-(-)-Fixolide
strong musk
The Nobel Prize in Physiology and Medicine 2004 for the discovery of
odorant receptors
Linda BuckRichard Axel
Species Number of OR genes
Man 396
Chimpanzee 399
Macaque 326
Mouse 1130
Rat 1207
Dog 811
Caw 1152
Opossum 1198
Chicken 300
Xenopus 1024
Zebra fish 155
Fugu 86
Drosophila 62
C.elegans 1278
Receptors operative in MOE
Receptors Ligands Origin Proposed functions
odorantGPCRs
N = 350-1300
trace amineGPCRN = 3-20
GC-D
N = 1
general odors
MHC class I
peptides
volatile amines
CO2
uroguanyline
guanylin
food
environment
urine
body secretions
urine
atmosphere
urine
odor recognition, discrimination,
attraction, repulsion
social recognition of
other strains
stress response
gender recognition
avoidance behavior
Detection of cues related to
hunger, satiety, or thirst
Curr
ent (p
A)
Time (s) Lilial (mM)
Pe
ak c
urr
en
t (p
A)
lilial
Electrical excitation of olfactory neurons by odorants
50 ms
50
5
2
0.5
0.1
0
cA
MP
-gate
d c
urr
ent
(pA
)
cAMP,m
-6
-5
-6
-4
-2
-6
-4
-2
-4
-2
0
-1
0
-1
0
AC transduction cascade in olfactory cilia
PDE1
ACIII
Odorant
Ca2+
Cl-
3Na+
1Ca2+
abg
Receptor
CaM
cAMP-gated channel
Arrestin
RKGolf
cAMP
CNGA2
PDE4
1Ca2+1Na+/ 2Cl-/1K+1K+
4Na+
Cl-in ~ 40-100 mM
Cl-out ~ 55-93 mM
Cineol, 300 mM
50 pA
1 sec
Cineol, 300 mM
3 mM Ca2+
3 mM Mg2+
, no Ca2+
A
B
Kurahashi & Shibuya, Brain Res., 1990
Adaptation of olfactory sensory neurons is mediated by Ca2+
Ca2+-dependent elements of the olfactory transduction cascade
PDE1
ACIII
Odorant
Ca2+
Cl-
3Na+
1Ca2+
abg
Receptor
CaM
cAMP-gated channel
Arrestin
RKGolf
cAMP
CNGA2
1Ca2+1Na+/ 2Cl-/1K+1K+
4Na+
CNGA2
CNGA4
CNGB1b
CaM siteCNBD
Olfactory CNG channel
After Trudeau & Zagotta, J.Biol.Chem. 2003
CNGA2CNGA2
CNGB1b CNGA4
CaM site
0.01 0.1 1 10 100 1000 10000
0.0
0.5
1.0
cAMP concentration, mM
Norm
aliz
ed o
pe
n p
rob
ab
ility
K1/2 = 1.4 mM K1/2 = 29 mM
Control Calmodulin
Odorant
receptors
Trace amine
receptors
Golf
ACIII
CNG2A
PDE4
Ciliary OMP-positive
Microvillar
OMP-negative
Receptor-GC
CNGA3
PDE2
?
TRPM5 gustducin
PLCb2
TRPM5
?
Population of chemosensory cells in MOE
GC-cGMP transduction cascade in olfactory cilia
PDE2
Guanylyl
cyclase-D
cGMP-gated channel
cGMP
CNGA3
DF
/F=
10%
50 s
0.4%
Hu et al., Science 2007
OSN
Leinders-Zufall et al., PNAS 2007
uroguanylin guanylin
Species Functionality of GC-D gene
Mouse +
Rat +
Treeshrew +
Lemur +
bushbaby +
Man -
Chimpanzee -
Macaque -
Orangutan -
Gorilla -
Baboon -
Agonist types
0.1 1 10 100 1000 10000
0
1
Ligand concentration
Norm
aliz
ed
resp
onse
Full agonist
Partial agonist
Inverse agonist
Antagonist
acetyl isoeugenol (1)
eugenol (EG) methyl isoeugenol (2)
allyl benzene (3)
isosafrole (4)
Odorant antagonism
Vassalli et al., Cell, 2002
Axons of M71-espressing OSN converge into two glomeruli
glomeruli
axons
Olfactory sensory
neurons
M71-LacZ transgenic mouse
Septal organ
Glueneberg ganglion
Vomeronasal organ
Main
olfactory
epithelium
Main
olfactory
bulb
Accessory
olfactory
bulb
BV
basal
apical
Compound Species Effect Olfactory subsystem
3-Amino-s-triazole Mouse Attracts females ?
2,5-Dimethylpyrazine Mouse Delays puberty VNO
in females
2-Heptanone Mouse Extends estrus VNO
4-Ethylphenol Mouse Attracts females and VNO
repels males
2-sec-Butyl-4,5-dihydrothiazole Mouse Attracts females and VNO
repels males; induces
2,3-Dehydro-exobrevicomin Mouse Attracts females and VNO
repels males; induces
2-Methylbut-2-enal Rabbit Attracts pups MOE
to nipples
Dimethyl disulfide Hamster Induces copulation VNO
in males
(Z)-7-Dodecenyl acetate Asian elephant Attracts males ?
5-a-Androst-16-en-3-one Pig Facilitates mating MOE
in females
Sodefrin Newt Attracts females VNO
apical
basal
Key signaling molecules identified in VNO neurons
Apical neurons:
V1R, Gi2, TRPC2
Basal neurons:
V2R, Go, TRPC2
V1R/V2R Pheromone
Transduction cascade in VNO neurons
a
bg
PIP2
IP3
DAGTRPC2
Ca2+
AA
AA-gated channel
CaM
DAG lipaseDAG
PLC
Gi2/G0
Species V1R V2R TRPC2
Man 5 (115) 0 (20) 0 (1)
Chimpanzee 0 (116) 0 (17) 0 (1)
Macaque ? 0 (11) ?
Mouse 187 (121) 121 (158) 1
Rat 106 (66) 79 (142) 1
Dog 8 (33) 0 (9) 1
Caw 40 (45) 0 (16) ?
Opossum 98 (30) 86 (79) ?
Number of genes (pseudogenes)
Volatile male
gender signal
Do chemical communications between humans exist?
After Spehr et al., Cell. Mol. Life Sci., 2006
Common odorants
Electronic nose applications
I. Medicine
1. Biological liquids analysis
2. Disease detection
II. Security
1. Detection of individuals
2. Detection of explosives and narcotics
3. Detection of poisons and toxins in air and water
4. Detection of bacterial contaminations
III. Crime Investigation
1. Detection of individuals
2. Detection of poisons and toxins in a victom body
3. Detection of bacterial contaminations
III. Food Industry
1. Analysis of food and drink quality
2. Detection of hazardous components
IV. Perfumery industry
1. Perfume quality control
2. New odor compositions
Odor detection
Sensory
information
processing
Odor
recognition
Olfactory sensory
neurons
Olfactory bulb Olfactory cortex
Decision
making
Brain
Odor
Information processing in olfactory system
Schematic diagram of an electronic nose
Sensor 1
Data
processing
pattern
recognition
**************
Odor Sensor 2
Sensor NData base
system
Decision
making
Input lightTransmitted
light
metal layer
sensing layer plasmon resonance
glass fiber
cladding
SPR sensor
odorant
Salmonella typhimurium
Streppneumonia
Shigellaflexneri
Salmonellaenteritidis
Hemophilusinfluenza
Enterococcusfaecalis
E. Coli O157E. Coli
Fresh Nutrient
Staph aureus Pseudomonasaeruginosa
Klebsiellapneumonia
VaporPrint analysis of Infectious Bacteria Cultures
Electric Sensor Technology
Salmonella typhimurium
Fresh Nutrient