Axin and the Axin/Arrow-binding protein DCAP mediate glucose-glycogen metabolism.
Axin was found as a negative regulator of the canonical Wnt pathway. Human LRP5 was originally found as a candidate gene of insulin dependent diabetes mellitus (IDDM), but its Drosophila homolog, Arrow, works as a co-receptor of the canonical Wnt signal. In our previous paper, we found a new Drosophila Axin (Daxin)-binding SH3 protein, DCAP, a homolog of mammalian CAV family protein. Among the subtypes, DCAPL3 shows significant homology with CAP, an essential component of glucose transport in insulin signal. Further binding assay revealed that DCAP binds to not only Axin but also Arrow, and Axin binds to not only GSK3beta but also Arrow. However, overexpression and RNAi experiments of DCAP do not affect the canonical Wnt pathway. As DCAP is expressed predominantly in insulin-target organs, and as RNAi of DCAP disrupts the pattern of endogenous glycogen accumulation in late stage embryos, we suggest that DCAP is also involved in glucose transport. Moreover, early stage embryos lacking maternal Axin show significant delay of initial glycogen decomposition, and RNAi of Axin in S2 cells revealed quite increase of endogenous glycogen level as well as GSK3beta. These results suggest that Axin and DCAP mediate glucose-glycogen metabolism in embryo. In addition, the interaction among Axin, Arrow, and DCAP implies a possible cross-talk between Wnt signal and insulin signal.
Yamazaki
Hiroto
H
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. hyamazaki@hms.harvard.edu
Yanagawa
Shin ichi
Si
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D060466:Axin Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004330:Drosophila / Q000196:embryology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000032:analysis / Q000378:metabolism*; D007328:Insulin / Q000502:physiology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction; D018411:Spodoptera
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C118000:Axn protein, Drosophila; C410502:Capt protein, Drosophila; D002352:Carrier Proteins; D029721:Drosophila Proteins; D007328:Insulin; D008840:Microfilament Proteins; D011956:Receptors, Cell Surface; C474373:arr protein, Drosophila; D006003:Glycogen; D005947:Glucose