scholarly journals LRP6 Receptor Plays Essential Functions in Development and Human Diseases

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 120
Author(s):  
Abdulmajeed Fahad Alrefaei ◽  
Muhammad Abu-Elmagd
Keyword(s):  
Biological Activities ◽  
Metastatic Cancer ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Model Systems ◽  
Human Diseases ◽  
Lipoprotein Receptor ◽  
Surface Receptors ◽  
Density Lipoprotein Receptor ◽  
Wnt Inhibitors

LRP6 is a member of the low-density lipoprotein receptor superfamily of cell-surface receptors. It is required for the activation of the Wnt/β-catenin signalling pathway. LRP6 is detected in different tissue types and is involved in numerous biological activities such as cell proliferation, specification, metastatic cancer, and embryonic development. LRP6 is essential for the proper development of different organs in vertebrates, such as Xenopus laevis, chickens, and mice. In human, LRP6 overexpression and mutations have been reported in multiple complex diseases including hypertension, atherosclerosis, and cancers. Clinical studies have shown that LRP6 is involved in various kinds of cancer, such as bladder and breast cancer. Therefore, in this review, we focus on the structure of LRP6 and its interactions with Wnt inhibitors (DKK1, SOST). We also discuss the expression of LRP6 in different model systems, with emphasis on its function in development and human diseases.

scholarly journals Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis

2010 ◽  
Vol 188 (6) ◽  
pp. 919-933 ◽  
Author(s):  
Marcel Mettlen ◽  
Dinah Loerke ◽  
Defne Yarar ◽  
Gaudenz Danuser ◽  
Sandra L. Schmid
Keyword(s):  
Dynamic Behavior ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Progressive Increase ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Coated Pits ◽  
Surface Receptors ◽  
Heterogeneous Dynamics ◽  
Density Lipoprotein Receptor

Clathrin-mediated endocytosis of surface receptors and their bound ligands (i.e., cargo) is highly regulated, including by the cargo itself. One of the possible sources of the observed heterogeneous dynamics of clathrin-coated pits (CCPs) might be the different cargo content. Consistent with this, we show that CCP size and dynamic behavior varies with low density lipoprotein receptor (LDLR) expression levels in a manner dependent on the LDLR-specific adaptors, Dab2 and ARH. In Dab2-mCherry–expressing cells, varying LDLR expression leads to a progressive increase in CCP size and to the appearance of nonterminal endocytic events. In LDLR and ARH-mCherry–expressing cells in addition to an increase in CCP size, turnover of abortive CCPs increases, and the rate of CCP maturation decreases. Altogether, our results underscore the highly dynamic and cargo-responsive nature of CCP assembly and suggest that the observed heterogeneity is, in part, related to compositional differences (e.g., cargo and adaptors) between CCPs.

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