Lipid modification in Wnt structure and function

Ke, Jiyuan; Xu, H. Eric; Williams, Bart O.

doi:10.1097/mol.0b013e32835df2bf

Cited by 21 publications

(25 citation statements)

References 45 publications

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“…Because of the homology between int-1 and Wingless, the gene was renamed Wnt1 (Wingless plus int1) [4] and was eventually recognized as the founding member of a large Wnt gene family. The Wnt proteins of molecular weight approximately 40,000 are cysteine-rich, glycosylated lipid-modified secreted proteins that regulate embryonic development, cell proliferation, differentiation, and migration [5], [6].…”

Section: Introductionmentioning

confidence: 99%

Role of the Wnt signaling molecules in the tooth

Tamura

Nemoto

2016

Japanese Dental Science Review

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SummaryWnt signaling plays a central role in many processes during embryonic development and adult homeostasis. At least 19 types of Wnt ligands, receptors, transducers, transcription factors, and antagonists have been identified in mammals. Two distinct Wnt signaling pathways, the canonical signaling pathway and the noncanonical signaling pathway, have been described. Some Wnt signaling pathway components are expressed in the dental epithelium and mesenchyme during tooth development in humans and mice. Functional studies and experimental analysis of relevant animal models confirm the effects of Wnt signaling pathway on the regulation of developing tooth formation and adult tooth homeostasis. Mutations in some Wnt signaling pathway components have been identified in syndromic and non-syndromic tooth agenesis. This review provides an overview of progress in elucidating the role of Wnt signaling pathway components in the tooth and the resulting possibilities for therapeutic development.

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Section: Introductionmentioning

confidence: 99%

Role of the Wnt signaling molecules in the tooth

Tamura

Nemoto

2016

Japanese Dental Science Review

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“…Because of the homology between int1 and Wingless , the gene was renamed as Wnt1 ( W ingless + i nt1 ) [5] and was eventually recognized as the founding member a large Wnt gene family encoded by 19 different genes in humans and mice. Wnt proteins share characteristics as cysteine-rich glycoproteins dependent on the addition of a lipid modification for function [6]. …”

Section: Introductionmentioning

confidence: 99%

Wnt signaling in bone and muscle

Rudnicki

Williams

2015

Bone

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117

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“…For secretion and effective signaling, Wnt proteins require a lipid modification that renders them hydrophobic and insoluble (Ke et al, 2013; Takada et al, 2006). The chaperone protein required for Wnt secretion is Wntless (Wls) (Banziger et al, 2006; Bartscherer et al, 2006; Goodman et al, 2006), a transmembrane protein that hides the lipid modification in a lipocalin fold and escorts the Wnt protein through the secretory pathway to the cell membrane (Das et al, 2012; Willert and Nusse, 2012).…”

Section: Introductionmentioning

confidence: 99%

Distinct requirements for Wntless in habenular development

Kuan

Roberson

Akitake

et al. 2015

Developmental Biology

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Secreted Wnt proteins play pivotal roles in development, including regulation of cell proliferation, differentiation, progenitor maintenance and tissue patterning. The transmembrane protein Wntless (Wls) is necessary for secretion of most Wnts and essential for effective Wnt signaling. During a mutagenesis screen to identify genes important for development of the habenular nuclei in the dorsal forebrain, we isolated a mutation in the sole wls gene of zebrafish and confirmed its identity with a second, independent allele. Early embryonic development appears normal in homozygous wls mutants, but they later lack the ventral habenular nuclei, form smaller dorsal habenulae and otic vesicles, have truncated jaw and fin cartilages and lack swim bladders. Activation of a reporter for β-catenin-dependent transcription is decreased in wls mutants, indicative of impaired signaling by the canonical Wnt pathway, and expression of Wnt-responsive genes is reduced in the dorsal diencephalon. Wnt signaling was previously implicated in patterning of the zebrafish brain and in the generation of left–right (L–R) differences between the bilaterally paired dorsal habenular nuclei. Outside of the epithalamic region, development of the brain is largely normal in wls mutants and, despite their reduced size, the dorsal habenulae retain L–R asymmetry. We find that homozygous wls mutants show a reduction in two cell populations that contribute to the presumptive dorsal habenulae. The results support distinct temporal requirements for Wls in habenular development and reveal a new role for Wnt signaling in the regulation of dorsal habenular progenitors.

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Lipid modification in Wnt structure and function

Abstract: The recent determination of the Wnt8-Fz8 structure has created new opportunities to better understand the mechanisms by which Wnt proteins activate downstream signaling pathways and has further clarified why lipid modification of Wnt is required for activation.

Cited by 21 publications

References 45 publications

Role of the Wnt signaling molecules in the tooth

Role of the Wnt signaling molecules in the tooth

Wnt signaling in bone and muscle

Distinct requirements for Wntless in habenular development

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