Olfactory receptor signaling is regulated by the
post-synaptic density 95, Drosophila discs large,
zona-occludens 1 (PDZ) scaffold multi-PDZ domain
protein 1
Ruth Dooley
1,2,
*, Sabrina Baumgart
2,
*, Sebastian Rasche
1
, Hanns Hatt
1
and Eva M. Neuhaus
3
1 Molecular Medicine Lab RCSI, Education & Research Centre Smurfit Building, Beaumont Hospital, Dublin, Republic of Ireland
2 Department of Cell Physiology, Ruhr University Bochum, Germany
3 NeuroScience Research Center, Charite
´
, Universita
¨
tsmedizin Berlin, Germany
Keywords
MUPP1; olfactory neuron; olfactory
receptor; PDZ protein; signal transduction
Correspondence
E. M. Neuhaus, NeuroScience Research
Center, Charite
´
, Universita
¨
tsmedizin Berlin,

Structured digital abstract
l
MINT-7290305: OR2AG1 (uniprotkb:Q9H205) physically interacts (MI:0915) with MUPP1
(uniprotkb:
O75970)byanti tag coimmunoprecipitation (MI:0007)
l
MINT-7289999, MINT-7290250, MINT-7290063, MINT-7290110: OR2AG1 (uni-
protkb:
Q9H205) binds (MI:0407)toMUPP1 (uniprotkb:O75970)bypeptide array (MI:0081)
l
MINT-7290162: mOR283-1 (uniprotkb:Q9D3U9) binds (MI:0407)toMUPP1 (uni-
protkb:
O75970)bypeptide array (MI:0081)
l
MINT-7290128: mOR-EG (uniprotkb:Q920P2) binds (MI:0407)toMUPP1 (uni-
protkb:
O75970)bypeptide array (MI:0081)
Abbreviations
CamKII, calcium ⁄ calmodulin-dependent protein kinase II; GABA
B
, c-aminobutyric acid receptor B; GFP, green fluorescent protein; GST,
glutathione S-transferase; HRP, horseradish peroxidase; INAD, inactivation no after potential D; MUPP1, multi-PDZ domain protein 1; OMP,
olfactory marker protein; OR, olfactory receptor; OSN, olfactory sensory neuron; PDZ, post-synaptic density 95, Drosophila discs large,
zona-occludens 1; RNAi, RNA interference; siRNA, small interfering RNA.
FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS 7279
Introduction
Detection of an odorant is initiated by activation of
a fraction of many hundreds of G protein-coupled
odorant receptors (ORs) expressed in olfactory sen-
sory neurons (OSNs) of the mammalian olfactory

cade, thereby bringing them into close proximity and
ensuring a rapid and specific signal transduction
[9,12].
PDZ domains are modular protein–protein interac-
tion domains, which are amongst the most abundant
protein interaction domains in organisms from bacteria
to mammals, and have been implicated in various pro-
cesses, including clustering, targeting and routing of
their binding partners [13–15]. PDZ target specificity is
usually dependent on the extreme carboxyl-terminal
amino acid sequence of the interacting protein; how-
ever, for some ligands, residues as far back as the )10
position may influence binding energy [16]. Peptide-
binding preferences of PDZ domains led to their
division into three discrete functional classes [16],
which may not be as strict as initially anticipated
because predictions of PDZ domain–peptide interac-
tions were recently shown to be evenly distributed
throughout selectivity space [17].
The multi-PDZ domain protein 1 (MUPP1) is com-
posed of thirteen PDZ domains, each diverse with
respect to its amino acid sequence. It was first identi-
fied through a yeast two-hybrid screening as an
interaction partner of the C-terminus of 5-hydroxy-
tryptamine receptor type 2C [18]. Subsequently, many
diverse interaction partners of MUPP1 have been
characterized, including G-protein coupled c-aminobu-
tyric acid receptor B (GABA
B
) [19] and the

MINT-7290191:hOR1D2 (uniprotkb:P34982) binds (MI:0407)toMUPP1 (uni-
protkb:
O75970)bypeptide array (MI:0081)
l
MINT-7289922: AC3 (uniprotkb:Q8VHH7) and MUPP1 (uniprotkb:O75970) colocalize
(
MI:0403)byfluorescence microscopy (MI:0416)
l
MINT-7289933, MINT-7289954, MINT-7289978:OR2AG1 (uniprotkb: Q9H205) binds
(
MI:0407)toMUPP1 (uniprotkb:O75970)bypull down (MI:0096)
PDZ proteins interact with olfactory receptors R. Dooley et al.
7280 FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS
expressed in the apical part of OSNs, mainly in the
cilia layer (Fig. 1C). Double immunolabeling showed
co-localization with adenylyl cyclase 3, a central mole-
cule in the olfactory signal transduction cascade in the
cilia of OSNs (Fig. 1C, D).
Interaction of PDZ domains 1 + 2 of MUPP1 with
OR2AG1 in vitro
PDZ domain interactions have been well characterized
and modes of binding have been grouped into three
main classes of PDZ binding motifs, occurring at the
C-terminus of the interacting proteins [16]. We scanned
the human olfactory receptor repertoire for putative
binding motifs and discovered them in the extreme
C-termini of approximately 30% of human ORs, with
examples from each of the three classes being outlined
to date (7% Class I, 12% Class II and 10% Class III;
Fig. 2A). Intriguingly, this suggested that a subset of

olfactory epithelium by RT-PCR. *Weak
band for ZO-1. (B) Fractional preparation of
whole olfactory epithelium shows MUPP1,
at 220 kDa, enriched in the cilia fraction (1)
compared to the remaining cell fractions
(2–4); a Coomassie-stained gel is shown as
a loading control. (C) MUPP1 is co-localized
with adenylyl cyclase 3 in the apical layer of
the olfactory epithelium. Immunohistochemi-
cal staining of 14 lm cryosections of
OMP-GFP mouse olfactory epithelium using
specific antibodies against MUPP1 (green)
and adenylyl cyclase 3 (red). Overlay shows
mature OSNs in blue. White arrow denotes
the apical layer. Scale bars = 50 lm. (D).
Higher magnification image of MUPP1 ⁄ ade-
nylyl cyclase 3 stained olfactory epithelium.
The arrow shows MUPP1 expression in cilia
and in dendritic knobs. Scale bar = 5 lm.
R. Dooley et al. PDZ proteins interact with olfactory receptors
FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS 7281
3 + 4, etc.) (Fig. 2C). Interaction assays were then
carried out by incubating different pairs of PDZ
domains as in vitro translation products with OR2AG1
C-terminus GST fusion peptides. A specific binding of
PDZ domains 1 + 2 was determined via western blot-
ting, whereas, for example, in vitro translated PDZ
domains 3 + 4 did not have the ability to bind to the
C-terminus of OR2AG1 (Fig. 2D). None of the PDZ
domains could bind to GST alone. We then tested

shown is representative of three independent immunoprecipitation experiments. (C) Western blot using HA-specific antibodies showing the
in vitro translation products of PDZ domain pairwise constructs. Three nonspecific bands appear at 170, 70 and 30 kDa. Specific bands at
the correct molecular weights are outlined (white asterisk). (D) PDZ domains 1 + 2 both interact with OR2AG1_GST in vitro. Interaction
assay using in vitro translated PDZ domains 1 + 2, PDZ domains 3 + 4, PDZ domain 1 and PDZ domain 2 with GST alone or C-terminus
OR2AG1_GST. The blots shown are representative of four independent experiments for each interaction assay described. (E) Peptide micro-
array with C-termini of different receptors incubated with PDZ domains 1 + 2 fused to HA; chemiluminescence detection on film after incu-
bation with a-HA antibodies and HRP-coupled secondary antibodies. The array shown is representative of four independent experiments;
peptide sequences for spots A1–A12 (row 1), A13–A24 (row 2) and B1 (FLAG tag) and B2 (HA tag, positive control) are listed in Table S1.
A1 and A2 serve as negative controls.
PDZ proteins interact with olfactory receptors R. Dooley et al.
7282 FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS
and mGluR2, as well as the olfactory cyclic nucleo-
tide-gated ion channel subunit A2, did not show any
interaction with the PDZ domains investigated.
We furthermore investigated the binding determi-
nants in the C-terminus of hOR2AG1 by spotting pep-
tides that correspond to mutated or shortened receptor
C-termini. Truncation of the last amino acids abol-
ished binding of the C-terminus of hOR2AG1 to PDZ
domains 1 + 2. hOR2AG1 constructs where the last
four amino acids H-S-T-L were mutated to H-A-T-A
[OR2AG1_deltaPDZ(A)] still bound to PDZ domains
1 + 2, whereas mutation to H-W-T-W [OR2AG1_del-
taPDZ(W)] completely abolished binding (Fig. 2E).
MUPP1 shows plasma membrane localization
upon co-expression of ORs
MUPP1 is a cytosolic protein, and MUPP1-GFP, simi-
lar to endogenous MUPP1, shows a homogenous,
predominantly cytosolic distribution when expressed
in Hana3A cells (Fig. 3A). Interestingly, when

GFP; at least five independent experiments were performed for each condition. (B) Higher magnification of the plasma membrane of the
cells shown in (A). (C) In vitro interaction properties of truncated hOR2AG1 C-terminus. Western blot showing HA-PDZ1 + 2 probed with
2AG1-GST and trunc8-GST, at 55 kDa, using a-HA antibodies. The experiment was repeated three times with similar results being obtained.
(D) Co-expression of hOR1D2 and hOR3A1 also resulted in translocation of MUPP1-GFP to the plasma membrane; at least five independent
experiments were performed for each receptor. Scale bars = 20 lm.
R. Dooley et al. PDZ proteins interact with olfactory receptors
FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS 7283
C-terminal mutant peptide was incubated with PDZ
domains 1 + 2 of MUPP1 and failed to interact with
truncated mutant (Fig. 3C).
Consistent with this observation is the fact that
other olfactory receptors showing interactions with
PDZ domains 1 + 2 (hOR1D2, hOR3A1) also caused
A
C
DE
FG
HI
B
Fig. 4. Functional role of MUPP1 in OR signaling. (A) Western blot showing MUPP1 expression in Hana3A cells (control) compared to 48
and 72 h after siRNA (exon5) transfection. (B) Representative ratiometric calcium imaging responses of transiently transfected Hana3A cells
[siRNA(1)]; the arrow represents the beginning of application of amylbutyrate, lasting for 10 s. (C) Western blot showing MUPP1 expression
in Hana3A cells (control) compared to scrambled siRNA, siRNA against exon 5 of MUPP1 and siRNA against exon 45 of MUPP1, 72 h after
transfection. (D) Bar chart showing the rise time (10–90%) of Hana3A cells responding to amylbutyrate, transfected with OR2AG1 (ctrl)
(n = 15) or siRNA(exon5)-treated Hana3A cells transfected with OR2AG1 (RNAi) (n = 15). (E) Time of decay from 90% of peak amplitude to
10% of average baseline (n = 15) for each condition and the percentage of cell responses decaying to basal levels within the time-frames
outlined. Cell responses not decaying within the time-frame of experiment were included in the > 20 s section; n = 15 for control, n =27
for RNAi(exon5). (F) Bar chart showing the rise time (10–90%) for siRNA(exon45) transfected Hana3A cells; n = 12 for control, n = 12 for
RNAi(exon45). (G) Bar chart showing the time of decay (90–10%) and percentages of cell responses for siRNA(exon45) transfected Hana3A
cells; n = 12 for control, n = 12 for RNAi(exon45). (H) Bar chart showing the rise time (10–90%) for Hana3A cells transfected with scrambled

control cells, 5.54 ± 0.87 s for RNA interference
(RNAi) compared to 4.27 ± 0.65 s for the control
(Fig. 4B, C). However, the response failed to decay
within the normal average time-frame in siRNA-trea-
ted cells (19.3 ± 2.9 s) compared to the control cells
(7.2 ± 2.1 s) (Fig. 4B, D). Using another siRNA
directed against an alternative exon of Mupp1, similar
results were obtained. The rise time of the OR-elicited
response was similar to that of the control cells
AB
CD
EF
Fig. 5. Interaction of MUPP1 with OR2AG1 is important for controlled signal decay. (A) Immunocytochemistry (a-HA antibody) showing sta-
ble expression of MUPP1-PDZ1 + 2-HA in Hana3A cells. Scale bar = 20 lm. (B) Representative ratiometric calcium imaging traces for
Hana3A cells (control) and MUPP1-PDZ1 + 2-HA cells (1 + 2) transiently transfected with OR2AG1. Arrows denote amylbutyrate application.
(C) Bar chart showing the rise time (10–90%) for Hana3A cells stably expressing MUPP1-PDZ1 + 2-HA, transiently transfected with
OR2AG1; n = 13 for control, n = 24 for PDZ domains 1 + 2. (D) Decay of response (90–10%) (n = 13 for control, n = 24 for PDZ domains
1 + 2) and the percentage of responses to amylbutyrate decaying to basal levels within the given time-frames. (E) Transient expression of a
truncated version of OR2AG1 missing the last eight amino acids (trunc8). Bar chart showing the rise time (10–90%) for Hana3A cells
expressing the truncated receptor (n = 12 for control, n = 17 for OR2AG1-trunc8). (F) Decay of response (90–10%) (n = 12 for control,
n = 17 for OR2AG1-trunc8) and the percentage of responses to amylbutyrate decaying to basal levels within the given time-frames. Error
bars show the SEM. **P < 0.01, ***P < 0.001.
R. Dooley et al. PDZ proteins interact with olfactory receptors
FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS 7285
(Fig. 4C), although the decay was prolonged signifi-
cantly (Fig. 4D). Cells transfected with a scrambled
version of the siRNA did not show any significant
differences in the kinetics of the OR-elicited
Ca
2+

2+
imaging
experiments. Truncation of the receptor from the
final eight amino acids (amino acids 309–316)
resulted in a prolonged signal decay, similar to that
observed in the siRNA experiments and in the cells
over-expressing PDZ domains 1 + 2, whereas the
rise time of the signals was again not affected
(Fig. 5E, F).
Discussion
Until now, the involvement of PDZ domain scaffold-
ing proteins in olfactory signal transduction has gone
unstudied. It has previously been suggested that such
scaffolding networks or ‘olfactosomes’ may exist [9,10]
but, to date, no evidence for this phenomenon has
been outlined. In the present study, we have uncovered
a PDZ protein as a novel interaction partner of olfac-
tory receptors and have elucidated the molecular
details of this interaction.
The primary source of olfactory signaling and the
sites of expression of ORs are the ciliary structures of
the OSNs. Interestingly, we found MUPP1 to be pre-
dominantly expressed in the apical compartment of
OSNs and enriched in the cilia fraction of a prepara-
tion of whole murine olfactory epithelium. We hypoth-
esize that MUPP1, through its multivalent capabilities,
could play a key role as a central nucleator of olfac-
tory signal transduction. With its thirteen PDZ
domains, each diverse in its amino acid sequence,
MUPP1 holds great potential for organizing signal

other membrane proteins [17]. We also found interac-
tion of PDZ domains 1 + 2 with ORs showing no
classical PDZ binding motifs, indicating that the
understanding of the exact molecular rules of OR
PDZ interaction will require further analysis. Previous
work with other proteins has already indicated that it
is highly likely that a large number of PDZ domain
interactions will not fit into the confined class defini-
tions and that PDZ domains may have been opti-
mized across the proteome in order to minimize
cross-reactivity [17].
We observed that a reduction of MUPP1 resulted in
a significant increase in the duration of Ca
2+
responses
evoked by the activation of recombinantly expressed
PDZ proteins interact with olfactory receptors R. Dooley et al.
7286 FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS
hOR2AG1. Similarly, over-expression of the OR-inter-
acting PDZ domains 1 + 2 of MUPP1 also resulted in
odorant-evoked Ca
2+
responses that persisted longer
than those in control cells. When over-expressed, PDZ
domains 1 + 2 may bind to the C-terminus of
hOR2AG1, thus having a blocking effect on the bind-
ing of the less abundant endogenous MUPP1. A trun-
cated receptor no longer containing a PDZ motif in
the C-terminus showed the same effect of prolonged
signal duration. Thus, all of the experiments revealed

signal of
ORs in the cilia of the sensory neurons, MUPP1 could
have a strong influence on the olfactory signaling path-
way. An interesting interaction partner of MUPP1 out-
lined to date is CamKII, which is known to play an
important role in olfactory adaptation [20]. By phos-
phorylation of adenylyl cyclase 3 in OSNs, CamKII
provides an important mechanism for the attenuation
of odorant-stimulated cAMP increases [31]. Alterna-
tively, because different pathways, such as those
involving phosphoinositide 3-kinase [32], are ultimately
engaged after OR stimulation, MUPP1 may control
OR activity by acting as a scaffold to link different
signaling pathways.
In conclusion, we have outlined a novel aspect of the
olfactory signal transduction cascade by uncovering a
previously unknown interaction partner of olfactory
receptors and a putative regulator of signaling
processes in OSNs. It is tempting to speculate that a
so-called ‘olfactosome’ exists in the cilia of olfactory
sensory neurons, organizing the vast array of signaling
molecules and ensuring the specificity of signaling.
How exactly MUPP1 could carry out such an impor-
tant task remains to be elucidated, although the answer
may lie in the remaining and as yet unidentified interac-
tion partners of MUPP1 in the olfactory sensory cell.
Experimental procedures
DNA constructs and primers
pCDNA3_MUPP1-GFP and in vitro translation tandem
PDZ domain constructs in vector pBAT were provided

bit polyclonal (Santa Cruz Biotechnology, Santa Cruz, CA,
USA), directly labeled using DyLightÔ549 Microscale
Antibody Labeling Kit (Pierce, Rockford, IL, USA); anti-
MUPP1, rabbit polyclonal (provided by H. Lu
¨
bbert, Ruhr-
University); anti-GFP, rabbit polyclonal (#ab290-50;
Abcam, Cambridge, MA, USA); a-HA antibody, mouse
monoclonal (#H9658; Sigma, St Louis, MO, USA). Second-
ary antibodies used were goat anti-rabbit Alexa546nm
R. Dooley et al. PDZ proteins interact with olfactory receptors
FEBS Journal 276 (2009) 7279–7290 ª 2009 The Authors Journal compilation ª 2009 FEBS 7287
(Molecular Probes, Carlsbad, CA, USA) and horseradish
peroxidase (HRP) coupled goat anti-mouse and goat anti-
rabbit IgGs (Bio-Rad, Hercules, CA, USA).
Cell culture and transfection
All tissue culture media and related reagents were purchased
from Invitrogen (Carlsbad, CA, USA). Hana3A cells [23]
(provided by H. Matsunami, Duke University Medical Cen-
ter, Durham, NC, USA), were maintained in DMEM plus
10% fetal bovine serum and 1% penicillin ⁄ streptomycin, at
37 °C and 5% CO
2
, and transfections were carried out using
a standard calcium phosphate precipitation technique.
MUPP1-GFP and OR plasmid DNAs were transfected in a
ratio of 1 : 10, with approximately 2 lg of total DNA per
dish. All images were acquired using a Zeiss LSM 510 Meta
confocal microscope (Carl Zeiss, Oberkochen, Germany).
Hana3A cells were stably transfected with pCMV ⁄ Bsd plas-

a mixture of 100 different odorant molecules (Henkel
KGaA, Du
¨
sseldorf, Germany) for specified amounts of
time. Control mice were housed in a separate room free
from artificial odorant stimulation. All mice were held in
standard cages at room temperature. Each cage was sur-
rounded by a Perspex chamber with ventilation suction to
maintain a constant air-flow.
GST fusion peptides and in vitro interaction
assays
The C-terminal region of OR2AG1 was found to lie between
amino acids 293 and 316, as predicted by tmhmm, a trans-
membrane helices prediction program based on a hidden
Markov model [34]. OR2AG1 C-terminus GST fusion pro-
teins and mutant construct thereof (trunc8-GST) were pro-
duced in Escherichia coli XL1 blue and purified on
glutathione sepharose beads (Becton-Dickinson Biosciences,
Franklin Lakes, NJ, USA). PDZ domains were in vitro trans-
lated using the TNTÒT3 Coupled Reticulocyte Lysate Sys-
tem (Promega, Madison, WI, USA). Interaction assays were
carried out by incubating 10 lLofin vitro translation prod-
uct with 50 lL of GST fusion peptide bead slurry for 2 h at
4 °C with gentle shaking. After a series of washing steps using
Buffer S (20 mm Hepes, 100 mm KCl, 0.5 mm EDTA, 1 mm
dithiothreitol, pH 7.9), specific interactions were assessed via
immunoblotting. GST alone was used as a negative control.
Peptide microarray
CelluSpotsÔ Peptide Arrays (Intavis AG, Cologne,
Germany) were blocked for 2 h at room temperature with

for heterologously expressed ORs [23,35,36], employing a
specialized microcapillary application system. The rise time
was calculated as the time in seconds from 10% of peak
response, starting from the average baseline value, to 90%
of peak amplitude. The response decay duration was calcu-
lated as the time in seconds between 90% and 10% of the
maximum amplitude.
Acknowledgements
We thank H. Bartel and J. Gerkrath for their excellent
technical assistance; H. Matsunami (Duke University
Medical Center, Durham, NC, USA) for the donation
of Hana3A cells; P. Mombaerts (MPI Biophysics,
Frankfurt, Germany) for the donation of OMP-GFP
transgenic mice; and H. Lu
¨
bbert ⁄ X. Zhu (Ruhr Uni-
versity, Bochum, Germany) for the donation of
MUPP1 antibodies and constructs. This work was sup-
ported by the International Max-Planck Research
School in Chemical Biology (IMPRS-CB), the Stud-
ienstiftung des deutschen Volkes, the Heinrich und
Anna Vogelsang Stiftung and the Deutsche Fors-
chungsgemeinschaft (SFB 642).
References
1 Buck L & Axel R (1991) A novel multigene family may
encode odorant receptors – a molecular-basis for odor
recognition. Cell 65, 175–187.
2 Bakalyar HA & Reed RR (1990) Identification of a
specialized adenylyl cyclase that may mediate odorant
detection. Science 250, 1403–1406.

odor detection: current views. Pflugers Archiv – Eur J
Physiol 441, 579–586.
12 Tsunoda S & Zuker CS (1999) The organization of
INAD-signaling complexes by a multivalent PDZ domain
protein in Drosophila photoreceptor cells ensures sensitiv-
ity and speed of signaling. Cell Calcium 26, 165–171.
13 Harris BZ & Lim WA (2001) Mechanism and role of
PDZ domains in signaling complex assembly. J Cell Sci
114, 3219–3231.
14 Nourry C, Grant SG & Borg JP (2003) PDZ domain
proteins: plug and play! Sci STKE 2003, RE7.
15 Sheng M & Sala C (2001) PDZ domains and the orga-
nization of supramolecular complexes. Ann Rev Neuro-
sci 24, 1–29.
16 Songyang Z, Fanning AS, Fu C, Xu J, Marfatia SM,
Chishti AH, Crompton A, Chan AC, Anderson JM &
Cantley LC (1997) Recognition of unique carboxyl-termi-
nal motifs by distinct PDZ domains. Science 275, 73–77.
17 Stiffler MA, Chen JR, Grantcharova VP, Lei Y, Fuchs
D, Allen JE, Zaslavskaia LA & MacBeath G (2007)
PDZ domain binding selectivity is optimized across the
mouse proteome. Science 317, 364–369.
18 Ullmer C, Schmuck K, Figge A & Lubbert H (1998)
Cloning and characterization of MUPP1, a novel PDZ
domain protein. FEBS Lett 424, 63–68.
19 Balasubramanian S, Fam SR & Hall RA (2007)
GABA(B) receptor association with the PDZ scaffold
Mupp1 alters receptor stability and function. J Biol
Chem 282, 4162–4171.
20 Krapivinsky G, Medina I, Krapivinsky L, Gapon S &

laevis oocytes. J Neurosci 19, 7426–7433.
27 Becamel C, Figge A, Poliak S, Dumuis A, Peles E,
Bockaert J, Lubbert H & Ullmer C (2001) Interaction
of serotonin 5-hydroxytryptamine type 2C receptors
with PDZ10 of the multi-PDZ domain protein MUPP1.
J Biol Chem 276, 12974–12982.
28 Tsunoda S, Sierralta J, Sun YM, Bodner R, Suzuki E,
Becker A, Socolich M & Zuker CS (1997) A multivalent
PDZ-domain protein assembles signalling complexes in
a g-protein-coupled cascade. Nature 388, 243–249.
29 Hardie RC & Raghu P (2001) Visual transduction in
Drosophila. Nature 413, 186–193.
30 Popescu DC, Ham AJL & Shieh BH (2006) Scaffolding
protein INAD regulates deactivation of vision by pro-
moting phosphorylation of transient receptor potential
by eye protein kinase C in Drosophila. J Neurosci 26,
8570–8577.
31 Wei J, Zhao AZ, Chan GC, Baker LP, Impey S, Beavo
JA & Storm DR (1998) Phosphorylation and inhibition
of olfactory adenylyl cyclase by CaM kinase II in neu-
rons: a mechanism for attenuation of olfactory signals.
Neuron 21, 495–504.
32 Spehr M, Wetzel CH, Hatt H & Ache BW (2002)
3-Phosphoinositides modulate cyclic nucleotide signaling
in olfactory receptor neurons. Neuron 33, 731–739.
33 Mashukova A, Spehr M, Hatt H & Neuhaus EM
(2006) beta-arrestin2-mediated internalization of
mammalian odorant receptors. J Neurosci 26, 9902–
9912.
34 Krogh A, Larsson B, von Heijne G & Sonnhammer EL