Mis-Assembly of Clathrin Lattices on Endosomes Reveals a Regulatory Switch for Coated Pit Formation

The clathrin-coated pit lattice is held onto the plasma membrane by an integral membrane protein that binds the clathrin AP-2 subunit with high affinity. In vitro studies have suggested that this protein controls the assembly of the pit because membrane bound AP-2 is required for lattice assembly. I...

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Bibliographic Details
Published in:The Journal of cell biology 1993-12, Vol.123 (5), p.1107-1117
Main Authors: Wang, Li-Hsien, Rothberg, Karen G., Richard G. W. Anderson
Format: Article
Language:English
Subjects:
Binding sites
Biological and medical sciences
Biological Transport - drug effects
Cations - pharmacology
Cell Membrane - drug effects
Cell Membrane - ultrastructure
Cell membranes
Cell physiology
Cells
Cells, Cultured
Cellular biology
Chlorpromazine - pharmacology
Clathrin - metabolism
Clathrin - ultrastructure
Coated Pits, Cell-Membrane - drug effects
Coated Pits, Cell-Membrane - metabolism
Coated Pits, Cell-Membrane - ultrastructure
Endocytosis
Endocytosis - drug effects
Endosomes
Fibroblasts
Fundamental and applied biological sciences. Psychology
Humans
Ice
Intracellular Membranes - drug effects
Intracellular Membranes - ultrastructure
LDL receptors
Membranes
Molecular and cellular biology
P branes
Proteins
Receptors
Receptors, LDL - drug effects
Receptors, LDL - ultrastructure
Recycling
Skin - cytology
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Description
Summary:The clathrin-coated pit lattice is held onto the plasma membrane by an integral membrane protein that binds the clathrin AP-2 subunit with high affinity. In vitro studies have suggested that this protein controls the assembly of the pit because membrane bound AP-2 is required for lattice assembly. If so, the AP-2 binding site must be a resident protein of the coated pit and recycle with other receptors that enter cells through this pathway. Proper recycling, however, would require the switching off of AP-2 binding to allow the binding site to travel through the endocytic pathway unencumbered. Evidence for this hypothesis has been revealed by the cationic amphiphilic class of drugs (CAD), which have previously been found to inhibit receptor recycling. Incubation of human fibroblasts in the presence of these drugs caused clathrin lattices to assemble on endosomal membranes and at the same time prevented coated pit assembly at the cell surface. These effects suggest that CADs reverse an on/off switch that controls AP-2 binding to membranes. We conclude that cells have a mechanism for switching on and off AP-2 binding during the endocytic cycle.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.123.5.1107