NDLI: Endosomal compartmentalization in three dimensions: implications for membrane fusion.

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Endosomal compartmentalization in three dimensions: implications for membrane fusion.

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Endosomal compartmentalization in three dimensions: implications for membrane fusion.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Murk, J. L. A. N. Posthuma, G. Humbel, B. M. Geuze, H. J. Ziese, U. Koster, A. J. Verkleij, A. J. Slot, J. W. Kleijmeer, M. J. Griffith, J. M.
Description	Author Affiliation: Murk JL ( Department of Cell Biology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.);
Abstract	Endosomes are major sorting stations in the endocytic route that send proteins and lipids to multiple destinations in the cell, including the cell surface, Golgi complex, and lysosomes. They have an intricate architecture of internal membrane structures enclosed by an outer membrane. Recycling proteins remain on the outer membrane, whereas proteins that are destined for degradation in the lysosome are sorted to the interior. Recently, a retrograde pathway was discovered whereby molecules, like MHC class II of the immune system, return from the internal structures to the outer membrane, allowing their further transport to the cell surface for T cell activation. Whether this return involves back fusion of free vesicles with the outer membrane, or occurs via the continuity of the two membrane domains, is an unanswered question. By electron tomography of cryo-immobilized cells we now demonstrate that, in multivesicular endosomes of B-lymphocytes and dendritic cells, the inner membranes are free vesicles. Hence, protein transport from inner to outer membranes cannot occur laterally in the plane of the membrane, but requires fusion between the two membrane domains. This implies the existence of an intracellular machinery that mediates fusion between the exoplasmic leaflets of the membranes involved, which is opposite to regular intracellular fusion between cytoplasmic leaflets. In addition, our 3D reconstructions reveal the presence of clathrin-coated areas at the cytoplasmic face of the outer membrane, known to participate in protein sorting to the endosomal interior. Interestingly, profiles reminiscent of inward budding vesicles were often in close proximity to the coats.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Endosomes Physiology Ultrastructure Membrane Fusion Animals B-Lymphocytes Cytology Cell Line Cell Line, Transformed Clathrin Metabolism Cytoplasm Dendritic Cells Freezing Microscopy, Immunoelectron T-Lymphocytes Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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