Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis

Summary: Clathrin-mediated endocytosis (CME) is critical for cellular signal transduction, receptor recycling, and membrane homeostasis in mammalian cells. Acute depletion of cholesterol disrupts CME, motivating analysis of CME dynamics in the context of human disorders of cholesterol metabolism. We...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ruthellen H. Anderson, Kem A. Sochacki, Harika Vuppula, Brandon L. Scott, Elizabeth M. Bailey, Maycie M. Schultz, Jason G. Kerkvliet, Justin W. Taraska, Adam D. Hoppe, Kevin R. Francis
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	cholesterol 7-dehydrocholesterol lipid metabolism sterols Smith-Lemli-Opitz syndrome membrane curvature Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6823a6fdb1ef451ca0e218e688d63346
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6823a6fdb1ef451ca0e218e688d63346
record_format	dspace
spelling	oai:doaj.org-article:6823a6fdb1ef451ca0e218e688d633462021-11-18T04:47:55ZSterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis2211-124710.1016/j.celrep.2021.110008https://doaj.org/article/6823a6fdb1ef451ca0e218e688d633462021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014868https://doaj.org/toc/2211-1247Summary: Clathrin-mediated endocytosis (CME) is critical for cellular signal transduction, receptor recycling, and membrane homeostasis in mammalian cells. Acute depletion of cholesterol disrupts CME, motivating analysis of CME dynamics in the context of human disorders of cholesterol metabolism. We report that inhibition of post-squalene cholesterol biosynthesis impairs CME. Imaging of membrane bending dynamics and the CME pit ultrastructure reveals prolonged clathrin pit lifetimes and shallow clathrin-coated structures, suggesting progressive impairment of curvature generation correlates with diminishing sterol abundance. Sterol structural requirements for efficient CME include 3′ polar head group and B-ring conformation, resembling the sterol structural prerequisites for tight lipid packing and polarity. Furthermore, Smith-Lemli-Opitz fibroblasts with low cholesterol abundance exhibit deficits in CME-mediated transferrin internalization. We conclude that sterols lower the energetic costs of membrane bending during pit formation and vesicular scission during CME and suggest that reduced CME activity may contribute to cellular phenotypes observed within disorders of cholesterol metabolism.Ruthellen H. AndersonKem A. SochackiHarika VuppulaBrandon L. ScottElizabeth M. BaileyMaycie M. SchultzJason G. KerkvlietJustin W. TaraskaAdam D. HoppeKevin R. FrancisElsevierarticlecholesterol7-dehydrocholesterollipid metabolismsterolsSmith-Lemli-Opitz syndromemembrane curvatureBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 7, Pp 110008- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cholesterol 7-dehydrocholesterol lipid metabolism sterols Smith-Lemli-Opitz syndrome membrane curvature Biology (General) QH301-705.5
spellingShingle	cholesterol 7-dehydrocholesterol lipid metabolism sterols Smith-Lemli-Opitz syndrome membrane curvature Biology (General) QH301-705.5 Ruthellen H. Anderson Kem A. Sochacki Harika Vuppula Brandon L. Scott Elizabeth M. Bailey Maycie M. Schultz Jason G. Kerkvliet Justin W. Taraska Adam D. Hoppe Kevin R. Francis Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis
description	Summary: Clathrin-mediated endocytosis (CME) is critical for cellular signal transduction, receptor recycling, and membrane homeostasis in mammalian cells. Acute depletion of cholesterol disrupts CME, motivating analysis of CME dynamics in the context of human disorders of cholesterol metabolism. We report that inhibition of post-squalene cholesterol biosynthesis impairs CME. Imaging of membrane bending dynamics and the CME pit ultrastructure reveals prolonged clathrin pit lifetimes and shallow clathrin-coated structures, suggesting progressive impairment of curvature generation correlates with diminishing sterol abundance. Sterol structural requirements for efficient CME include 3′ polar head group and B-ring conformation, resembling the sterol structural prerequisites for tight lipid packing and polarity. Furthermore, Smith-Lemli-Opitz fibroblasts with low cholesterol abundance exhibit deficits in CME-mediated transferrin internalization. We conclude that sterols lower the energetic costs of membrane bending during pit formation and vesicular scission during CME and suggest that reduced CME activity may contribute to cellular phenotypes observed within disorders of cholesterol metabolism.
format	article
author	Ruthellen H. Anderson Kem A. Sochacki Harika Vuppula Brandon L. Scott Elizabeth M. Bailey Maycie M. Schultz Jason G. Kerkvliet Justin W. Taraska Adam D. Hoppe Kevin R. Francis
author_facet	Ruthellen H. Anderson Kem A. Sochacki Harika Vuppula Brandon L. Scott Elizabeth M. Bailey Maycie M. Schultz Jason G. Kerkvliet Justin W. Taraska Adam D. Hoppe Kevin R. Francis
author_sort	Ruthellen H. Anderson
title	Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis
title_short	Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis
title_full	Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis
title_fullStr	Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis
title_full_unstemmed	Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis
title_sort	sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6823a6fdb1ef451ca0e218e688d63346
work_keys_str_mv	AT ruthellenhanderson sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT kemasochacki sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT harikavuppula sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT brandonlscott sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT elizabethmbailey sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT mayciemschultz sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT jasongkerkvliet sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT justinwtaraska sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT adamdhoppe sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis AT kevinrfrancis sterolslowerenergeticbarriersofmembranebendingandfissionnecessaryforefficientclathrinmediatedendocytosis
_version_	1718425043628720128

Sterols lower energetic barriers of membrane bending and fission necessary for efficient clathrin-mediated endocytosis

Ejemplares similares