LDL transcytosis by protein membrane diffusion.
Endothelial cell (EC) cultures of different, selected vascular beds and/or organs were screened for receptor-mediated transport of proteins with a semipermeable filter assay. In SVEC4-10 cells, a mouse lymphoid endothelial cell line, orosomucoid, albumin, insulin and LDL were transcytosed from the apical (luminal) to basal (abluminal) side by a receptor-mediated pathway. Specific LDL transcytosis involved transport of intact LDL. A pathway of degradation of LDL and basal release involved vesicles in transport to lysosomes and amino acid merocrine secretion. This newly described transcellular passage of LDL via lysosomes, as well as the standard pathway, were reduced to 70% by PEG(50)-cholesterol (PEG-Chol). Combined results of temperature-dependence analysis and PEG(50)-cholesterol sensitivity show that two pathways contribute to general LDL transcellular passage. We suggest a mechanism of domain hopping by protein membrane diffusion of receptors as the pathway for intact LDL delivery. Based on theoretical considerations we propose that active transport by protein membrane diffusion can be facilitated by an organizational structure of lipid microdomains and polar cellular organization.
Kuzmenko
Elena S
ES
Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Djafarzadeh
Siamak
S
Cakar
Z Petek
ZP
Fiedler
Klaus
K
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000737:chemistry / Q000378:metabolism*; D004058:Diffusion; D042783:Endothelial Cells / Q000502:physiology* / Q000648:ultrastructure; D000077614:Golgi Matrix Proteins; D008247:Lysosomes / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000494:pharmacology; D018110:Receptors, Lipoprotein / Q000037:antagonists & inhibitors / Q000378:metabolism; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D008078:Cholesterol, LDL; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; D033921:Vesicular Transport Proteins; C032531:apolipoprotein B,E receptor; C118255:polyethylene glycol-cholesterol; C091580:vesicular transport factor p115; D011092:Polyethylene Glycols; D002784:Cholesterol