<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Characterization of developmental role and mechanistic function of Kremen proteins"^^ . "The Wnt/beta-catenin signaling pathway plays pivotal roles during embryonic development and adult tissue homeostasis; these include the regulation of cell fate decisions during germ layer induction, axial patterning and organogenesis, as well as cell proliferation and stem cell maintenance. Wnt signaling is antagonized by Dickkopf (Dkk) proteins, which play an important role in antero-posterior patterning of the central nervous system. Dkks function by inhibiting the Wnt receptor LRP5/6. They act in conjunction with transmembrane proteins of the Kremen family (Krm1 and 2, collectively termed Krms). Dkk binds to both LRP5/6 and Krm and induces formation of a ternary complex, which is cleared from the cell surface by endocytosis, leading to shut down of Wnt signal transduction. This study was initiated by several open questions: How do Krms function to mediate LRP6 clearance from the cell surface? Are there other proteins involved in this process? Do Krms have Dkk-independent roles during Xenopus development? Towards a mechanistic analysis of Krm/Dkk mediated Wnt inhibition, several screens for Krm interaction/binding partners were undertaken which led to the identification and characterization of Erlectin, a novel secreted protein which (i) binds to N-glycans linked to Krm2; (ii) is a member of the endoplasmic reticulum (ER) synexpression group in Xenopus; (iii) is localized in the ER lumen; and (iv) is essential for normal Xenopus development. As a second major result of this study, I observed and established that Krm2 plays a Dkk1-independent role during Xenopus neural crest formation. The experimental data revealed that Krm2 (i) is co-expressed with Wnts and regulated by zygotic Wnt signaling; (ii) shows differential expression in the neural crest and can induce neural crest tissue when overexpressed; (iii) is required for neural crest formation; and (iv) promotes cell surface localization of LRP6, as well as LRP6-mediated Wnt signaling in cultured cells. Based on these findings I developed a model in which Krms may be considered as context-dependent inhibitors or activators of Wnt/LRP6 signaling, which are regulated by the presence or absence of Dkk, respectively. "^^ . "2007" . . . . . . . . "Christine"^^ . "Hassler"^^ . "Christine Hassler"^^ . . . . . . "Characterization of developmental role and mechanistic function of Kremen proteins (PDF)"^^ . . . "thesis8correctedFinal.pdf"^^ . . . "Characterization of developmental role and mechanistic function of Kremen proteins (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Characterization of developmental role and mechanistic function of Kremen proteins (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Characterization of developmental role and mechanistic function of Kremen proteins (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Characterization of developmental role and mechanistic function of Kremen proteins (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Characterization of developmental role and mechanistic function of Kremen proteins (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #7399 \n\nCharacterization of developmental role and mechanistic function of Kremen proteins\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .