Membrane Bound Axin Is Sufficient for Wingless Signaling in Drosophila Embryos

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Membrane Bound Axin Is Sufficient for Wingless Signaling in Drosophila Embryos Powered By Docstoc
					Copyright Ó 2009 by the Genetics Society of America
DOI: 10.1534/genetics.108.098236




                                                                    Note
                 Membrane Bound Axin Is Sufficient for Wingless Signaling
                               in Drosophila Embryos

                                                           Nicholas S. Tolwinski1
     Program in Developmental Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10065
                                                       Manuscript received November 2, 2008
                                                      Accepted for publication January 2, 2009


                                                          ABSTRACT
                The Wingless signaling pathway controls various developmental processes in both vertebrates and
             invertebrates. Here I probe the requirement for nuclear localization of APC2 and Axin in the Wg signal
             transduction pathway during embryonic development of Drosophila melanogaster. I find that nuclear
             localization of APC2 appears to be required, but Axin can block signaling when tethered to the
             membrane. These results support the model where Axin regulates Armadillo localization and activity in
             the cytoplasm.




T    HE Wnt/Wingless (Wg) signaling pathway plays
      essential roles in the development of animals.
Aspects of signaling regulate cell proliferation, differen-
                                                                            Tolwinski and Wieschaus 2004b). Other approaches
                                                                            showed that the membrane localization of the degrada-
                                                                            tion complex was a key step in signaling as GSK3 and CKI
tiation, polarity, and survival. Importantly, Wg pathway                    potentiated signaling at the membrane by phosporylat-
components have been found to affect stem cell main-                        ing LRP (Davidson et al. 2005; Zeng et al. 2005). Other,
tenance and tumor progression. The basic step in signal                     somewhat contradictory findings were that Axin was
transduction through this pathway is the regulation of                      required in the nucleus for pathway activation (Cong
Armadillo/b-catenin (Arm/b-cat) levels. In the absence                      and Varmus 2004; Wiechens et al. 2004). Another
of extracellular ligand, a degradation complex consist-                     important finding was that APC, a component of the
ing of the scaffold proteins Axin and APC and the kinases                   degradation complex, was shown to function in nuclear
CKI and Zw3 (Shaggy, GSK3) forms. This complex                              export of Arm (Rosin-Arbesfeld et al. 2000), and in
mediates the phosphorylation of Arm, tagging it for                         opposing transcriptional activation by the Arm/TCF
proteasome-mediated degradation. Upon ligand bind-                          complex (Sierra et al. 2006).
ing, the receptor complex of Frizzled (Fz) and Arrow                           Here I report that membrane-tethered Axin is suffi-
(LRP5/6, Arr) activates Disheveled (Dsh), which in turn                     cient for the proper transduction of Wg signal in the
inhibits the degradation complex leading to increased                       patterning of the Drosophila embryo. In contrast,
Arm protein levels. Arm in turn translocates to the                         membrane-tethered APC2 does not rescue signaling.
nucleus where it activates transcription in conjunction
with the transcription factor TCF (Logan and Nusse
2004).                                                                                     MATERIALS AND METHODS
   Previous results suggested a model where ligand-
mediated receptor activation recruited Axin to the                             Alleles used: axinS044230 (Hamada et al. 1999), apc1Q8 (Ahmed
                                                                            et al. 1998), apc2d40 (McCartney et al. 1999), and zw3M11-1
membrane where it bound Arr in a larger complex with                        (Perrimon and Smouse 1989). Please see Flybase for details of
Dsh and Fz. It was further shown that Axin was the rate-                    alleles.
limiting component, and its levels were regulated                              Crosses for the third chromosome (Ch.) mutants:
through proteasomal degradation in a signal-dependent                       (Ch. 3-left arm) da-GAL4, (Ch. 3-right arm) FRT 82B, axinS044230/
manner (Lee et al. 2003; Tolwinski et al. 2003;                               TM3
                                                                            (3L) da-GAL4, (3R) FRT 82B, apc1Q8, apc2d40/TM3
                                                                            (3L) da-GAL4, (3R) FRT 82B, apc1Q8, apc2d40, axinS044230/TM3.
  1
   Address for correspondence: Sloan-Kettering Institute, Memorial Sloan-      T
				
DOCUMENT INFO
Description: The Wingless signaling pathway controls various developmental processes in both vertebrates and invertebrates. Here I probe the requirement for nuclear localization of APC2 and Axin in the Wg signal transduction pathway during embryonic development of Drosophila melanogaster. I find that nuclear localization of APC2 appears to be required, but Axin can block signaling when tethered to the membrane. These results support the model where Axin regulates Armadillo localization and activity in the cytoplasm. [PUBLICATION ABSTRACT]
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