Endocytic receptor-mediated control of morphogen signaling

Willnow, Thomas E.; Christ, Annabel; Hammes, Annette

doi:10.1242/dev.084467

Cited by 27 publications

(26 citation statements)

References 92 publications

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“…Prominent examples of endocytic gateways for membrane receptors include clathrin-dependent as well as clathrin-independent pathways, which in different ways regulate the extent and duration of signal transduction, such as through the degradation and recycling of internalized receptors and in the formation of endosome-specific signaling complexes [56,57]. As will be discussed below, the CiPo constitutes a potent site for regulating such events during ciliamediated signaling.…”

Section: The Ciliary Pocket: a Specialized Site For Endo-and Exocytosismentioning

confidence: 99%

Endocytic Control of Cellular Signaling at the Primary Cilium

Pedersen

Mogensen

Christensen

2016

Trends in Biochemical Sciences

101

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Section: The Ciliary Pocket: a Specialized Site For Endo-and Exocytosismentioning

confidence: 99%

Endocytic Control of Cellular Signaling at the Primary Cilium

Pedersen

Mogensen

Christensen

2016

Trends in Biochemical Sciences

101

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“…The sequence and structure of its extracellular domain are similar to those of Lrp5 and Lrp6. Since the Lrp4 intracellular domain lacks some of the motifs in Lrp5 and Lrp6 known to be essential for Wnt co-receptor function, Lrp4 was proposed to be a negative regulator of Wnt signaling (Herz and Bock, 2002;Johnson et al, 2005;Weatherbee et al, 2006;Willnow et al, 2012). Supporting this idea, overexpression of Lrp4 results in decreased Wnt/β-catenin signaling activity in cultured cells (Johnson et al, 2005;Li et al, 2010;Ohazama et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

Multiple modes of Lrp4 function in modulation of Wnt/β-catenin signaling during tooth development

et al. 2017

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During development and homeostasis, precise control of Wnt/β-catenin signaling is in part achieved by secreted and membrane proteins that negatively control activity of the Wnt co-receptors Lrp5 and Lrp6. Lrp4 is related to Lrp5/6 and is implicated in modulation of Wnt/β-catenin signaling, presumably through its ability to bind to the Wise (Sostdc1)/sclerostin (Sost) family of Wnt antagonists. To gain insights into the molecular mechanisms of Lrp4 function in modulating Wnt signaling, we performed an array of genetic analyses in murine tooth development, where Lrp4 and Wise play important roles. We provide genetic evidence that Lrp4 mediates the Wnt inhibitory function of Wise and also modulates Wnt/β-catenin signaling independently of Wise. Chimeric receptor analyses raise the possibility that the Lrp4 extracellular domain interacts with Wnt ligands, as well as the Wnt antagonists. Diverse modes of Lrp4 function are supported by severe tooth phenotypes of mice carrying a human mutation known to abolish Lrp4 binding to Sost. Our data suggest a model whereby Lrp4 modulates Wnt/β-catenin signaling via interaction with Wnt ligands and antagonists in a context-dependent manner.

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“…The low-density lipoprotein receptor-related protein (LRP) 2 is a member of the LDL receptor gene family, a group of structurally related cell surface receptors with important roles in embryonic development (reviewed in Willnow et al, 2012). Earlier, we uncovered the function of LRP2 as an auxiliary sonic hedgehog (SHH) receptor required for mammalian forebrain formation .…”

Section: Introductionmentioning

confidence: 99%

LRP2 Acts as SHH Clearance Receptor to Protect the Retinal Margin from Mitogenic Stimuli

et al. 2015

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During forebrain development, LRP2 promotes morphogen signaling as an auxiliary SHH receptor. However, in the developing retina, LRP2 assumes the opposing function, mediating endocytic clearance of SHH and antagonizing morphogen action. LRP2-mediated clearance prevents spread of SHH activity from the central retina into the retinal margin to protect quiescent progenitor cells in this niche from mitogenic stimuli. Loss of LRP2 in mice increases the sensitivity of the retinal margin for SHH, causing expansion of the retinal progenitor cell pool and hyperproliferation of this tissue. Our findings document the ability of LRP2 to act, in a context-dependent manner, as activator or inhibitor of the SHH pathway. Our current findings uncovered LRP2 activity as the molecular mechanism imposing quiescence of the retinal margin in the mammalian eye and suggest SHH-induced proliferation of the retinal margin as cause of the large eye phenotype observed in mouse models and patients with LRP2 defects.

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Endocytic receptor-mediated control of morphogen signaling

Cited by 27 publications

References 92 publications

Endocytic Control of Cellular Signaling at the Primary Cilium

Endocytic Control of Cellular Signaling at the Primary Cilium

Multiple modes of Lrp4 function in modulation of Wnt/β-catenin signaling during tooth development

LRP2 Acts as SHH Clearance Receptor to Protect the Retinal Margin from Mitogenic Stimuli

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