Draft:Low-density lipoprotein receptor-related protein 6

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Declined by Ktkvtsh 4 seconds ago. Last edited by Ktkvtsh 4 seconds ago. Reviewer: Inform author.

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Submission declined on 29 August 2024 by KylieTastic (talk).

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Declined by KylieTastic 2 hours ago.

Low-density lipoprotein receptor-related protein 6 (LRP6), is a protein that in humans is encoded by the LRP6 gene. LRP6 is a member of the low-density lipoprotein (LDLR) superfamily of cell-surface receptors family. It is a single-span transmembrane protein essential for the activation of Wnt/β-catenin signaling pathway.^[1]^[2] LRP6 consists of four YWTD β-propeller domains, each of which is followed by an EGF-like domain, and this is followed by three LDLR type A repeats, a transmembrane helix, and a short intracellular domain.^[3]

Genetic Mutations

A LRP6 mutant lacking the intracellular domain is defective in Wnt signaling^[4] while LRP6 mutant lacking the extracellular domain (but anchored on the membrane) are constitutively active.^[5]

Common genetic variants of LRP6 have been associated with the risks for hyperlipidemia,^[6] atherosclerosis,^[7] coronary disease,^[8] and late-onset Alzheimer's disease^[9] in the general population.

References

^ Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, He X (January 2004). "A Mechanism for Wnt Coreceptor Activation". Molecular Cell. 13 (1): 149–156. doi:10.1016/S1097-2765(03)00484-2.
^ MacDonald BT, He X (1 December 2012). "Frizzled and LRP5/6 Receptors for Wnt/ -Catenin Signaling". Cold Spring Harbor Perspectives in Biology. 4 (12): a007880–a007880. doi:10.1101/cshperspect.a007880.
^ Cheng Z, Biechele T, Wei Z, Morrone S, Moon RT, Wang L, Xu W (November 2011). "Crystal structures of the extracellular domain of LRP6 and its complex with DKK1". Nature Structural & Molecular Biology. 18 (11): 1204–1210. doi:10.1038/nsmb.2139.
^ Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X (September 2000). "LDL-receptor-related proteins in Wnt signal transduction". Nature. 407 (6803): 530–535. doi:10.1038/35035117.
^ Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C (17 May 2001). "LDL-receptor-related protein 6 is a receptor for Dickkopf proteins". Nature. 411 (6835): 321–325. doi:10.1038/35077108.
^ Tomaszewski M, Charchar FJ, Barnes T, Gawron-Kiszka M, Sedkowska A, Podolecka E, Kowalczyk J, Rathbone W, Kalarus Z, Grzeszczak W, Goodall AH, Samani NJ, Zukowska-Szczechowska E (September 2009). "A Common Variant in Low-Density Lipoprotein Receptor–Related Protein 6 Gene (LRP6) Is Associated With LDL-Cholesterol". Arteriosclerosis, Thrombosis, and Vascular Biology. 29 (9): 1316–1321. doi:10.1161/ATVBAHA.109.185355.
^ Sarzani R, Salvi F, Bordicchia M, Guerra F, Battistoni I, Pagliariccio G, Carbonari L, Dessì-Fulgheri P, Rappelli A (February 2011). "Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant". Nutrition, Metabolism and Cardiovascular Diseases. 21 (2): 150–156. doi:10.1016/j.numecd.2009.08.004.
^ Mani A, Radhakrishnan J, Wang H, Mani A, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP (2 March 2007). "LRP6 Mutation in a Family with Early Coronary Disease and Metabolic Risk Factors". Science. 315 (5816): 1278–1282. doi:10.1126/science.1136370.
^ De Ferrari GV, Papassotiropoulos A, Biechele T, Wavrant De-Vrieze F, Avila ME, Major MB, Myers A, Sáez K, Henríquez JP, Zhao A, Wollmer MA, Nitsch RM, Hock C, Morris CM, Hardy J, Moon RT (29 May 2007). "Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease". Proceedings of the National Academy of Sciences. 104 (22): 9434–9439. doi:10.1073/pnas.0603523104.

[1] Tamai K, Zeng X, Liu C, Zhang X, Harada Y, Chang Z, He X (January 2004). "A Mechanism for Wnt Coreceptor Activation". Molecular Cell. 13 (1): 149–156. doi:10.1016/S1097-2765(03)00484-2.

[2] MacDonald BT, He X (1 December 2012). "Frizzled and LRP5/6 Receptors for Wnt/ -Catenin Signaling". Cold Spring Harbor Perspectives in Biology. 4 (12): a007880–a007880. doi:10.1101/cshperspect.a007880.

[3] Cheng Z, Biechele T, Wei Z, Morrone S, Moon RT, Wang L, Xu W (November 2011). "Crystal structures of the extracellular domain of LRP6 and its complex with DKK1". Nature Structural & Molecular Biology. 18 (11): 1204–1210. doi:10.1038/nsmb.2139.

[4] Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP, He X (September 2000). "LDL-receptor-related proteins in Wnt signal transduction". Nature. 407 (6803): 530–535. doi:10.1038/35035117.

[5] Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, Niehrs C (17 May 2001). "LDL-receptor-related protein 6 is a receptor for Dickkopf proteins". Nature. 411 (6835): 321–325. doi:10.1038/35077108.

[6] Tomaszewski M, Charchar FJ, Barnes T, Gawron-Kiszka M, Sedkowska A, Podolecka E, Kowalczyk J, Rathbone W, Kalarus Z, Grzeszczak W, Goodall AH, Samani NJ, Zukowska-Szczechowska E (September 2009). "A Common Variant in Low-Density Lipoprotein Receptor–Related Protein 6 Gene (LRP6) Is Associated With LDL-Cholesterol". Arteriosclerosis, Thrombosis, and Vascular Biology. 29 (9): 1316–1321. doi:10.1161/ATVBAHA.109.185355.

[7] Sarzani R, Salvi F, Bordicchia M, Guerra F, Battistoni I, Pagliariccio G, Carbonari L, Dessì-Fulgheri P, Rappelli A (February 2011). "Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant". Nutrition, Metabolism and Cardiovascular Diseases. 21 (2): 150–156. doi:10.1016/j.numecd.2009.08.004.

[8] Mani A, Radhakrishnan J, Wang H, Mani A, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP (2 March 2007). "LRP6 Mutation in a Family with Early Coronary Disease and Metabolic Risk Factors". Science. 315 (5816): 1278–1282. doi:10.1126/science.1136370.

[9] De Ferrari GV, Papassotiropoulos A, Biechele T, Wavrant De-Vrieze F, Avila ME, Major MB, Myers A, Sáez K, Henríquez JP, Zhao A, Wollmer MA, Nitsch RM, Hock C, Morris CM, Hardy J, Moon RT (29 May 2007). "Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease". Proceedings of the National Academy of Sciences. 104 (22): 9434–9439. doi:10.1073/pnas.0603523104.

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