PURPOSE OF REVIEW: Long-term exposure to elevated concentrations of LDL cholesterol increases the risk of cardiovascular events. The main player in clearing LDL cholesterol is the LDL receptor (LDLR) trafficking pathway; however, our fundamental knowledge about the mechanisms regulating this pathway is still incomplete. RECENT FINDINGS: The LDLR pathway is very complex and involves multiple proteins. Endocytosis is regulated by two different adaptor proteins, that is, autosomal recessive hypercholesterolemia and Disabled-2. The proteolysis of the LDLR is regulated by inducible degrader of the LDLR and proprotein convertase subtilisin/kexin type 9. However, only a few proteins have been identified that provide insights into the endosomal sorting and recycling of the LDLR. SUMMARY: Since the discovery of LDLR, knowledge about its function has greatly expanded. As a result of its importance in maintaining homeostatic LDL levels, the LDLR pathway has emerged as a key therapeutic target to reduce circulating cholesterol. In order to be able to treat and diagnose individuals with hypercholesterolemia in the future, it is important to learn more about the LDLR trafficking pathway, as we still lack a full mechanistic understanding of how LDLR trafficking is controlled.
PURPOSE OF REVIEW: Long-term exposure to elevated concentrations of LDL cholesterol increases the risk of cardiovascular events. The main player in clearing LDL cholesterol is the LDL receptor (LDLR) trafficking pathway; however, our fundamental knowledge about the mechanisms regulating this pathway is still incomplete. RECENT FINDINGS: The LDLR pathway is very complex and involves multiple proteins. Endocytosis is regulated by two different adaptor proteins, that is, autosomal recessive hypercholesterolemia and Disabled-2. The proteolysis of the LDLR is regulated by inducible degrader of the LDLR and proprotein convertase subtilisin/kexin type 9. However, only a few proteins have been identified that provide insights into the endosomal sorting and recycling of the LDLR. SUMMARY: Since the discovery of LDLR, knowledge about its function has greatly expanded. As a result of its importance in maintaining homeostatic LDL levels, the LDLR pathway has emerged as a key therapeutic target to reduce circulating cholesterol. In order to be able to treat and diagnose individuals with hypercholesterolemia in the future, it is important to learn more about the LDLR trafficking pathway, as we still lack a full mechanistic understanding of how LDLR trafficking is controlled.
Authors: Paulina Bartuzi; Daniel D Billadeau; Robert Favier; Shunxing Rong; Daphne Dekker; Alina Fedoseienko; Hille Fieten; Melinde Wijers; Johannes H Levels; Nicolette Huijkman; Niels Kloosterhuis; Henk van der Molen; Gemma Brufau; Albert K Groen; Alison M Elliott; Jan Albert Kuivenhoven; Barbara Plecko; Gernot Grangl; Julie McGaughran; Jay D Horton; Ezra Burstein; Marten H Hofker; Bart van de Sluis Journal: Nat Commun Date: 2016-03-11 Impact factor: 14.919
Authors: Valentin Schlegel; Theresa Treuner-Kaueroff; Daniel Seehofer; Thomas Berg; Susen Becker; Uta Ceglarek; Joachim Thiery; Thorsten Kaiser Journal: PLoS One Date: 2017-07-20 Impact factor: 3.240