title: The architectural relationship of components controlling mast cell endocytosis.
abstract: Eukaryotic cells use multiple routes for receptor internalization. Here, we examine the topographical relationships of clathrin-dependent and clathrin-independent endocytic structures on the plasma membranes of leukemia-derived mast cells. The high affinity IgE receptor (FcεRI) utilizes both pathways, whereas transferrin receptor serves as a marker for the classical clathrin-mediated endocytosis pathway. Both receptors were tracked by live-cell imaging in the presence or absence of inhibitors that established their differential dependence on specific endocytic adaptor proteins. The topology of antigen-bound FcεRI, clathrin, dynamin, Arf6 and Eps15-positive structures were analyzed by 2D and 3D immunoelectron microscopy techniques, revealing their remarkable spatial relationships and unique geometry. We conclude that the mast cell plasma membrane has multiple specialized domains for endocytosis. Their close proximity might reflect shared components, such as lipids and adaptor proteins, that facilitate inward membrane curvature. Intersections between these specialized domains might represent sorting stations that direct cargo to specific endocytic pathways.
authors.affiliation: Department of Pathology University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
authors.forename: Cédric
authors.initials: C
authors.lastname: Cleyrat
authors.forename: Anza
authors.initials: A
authors.lastname: Darehshouri
authors.forename: Karen L
authors.initials: KL
authors.lastname: Anderson
authors.forename: Christopher
authors.initials: C
authors.lastname: Page
authors.forename: Diane S
authors.initials: DS
authors.lastname: Lidke
authors.forename: Niels
authors.initials: N
authors.lastname: Volkmann
authors.forename: Dorit
authors.initials: D
authors.lastname: Hanein
authors.forename: Bridget S
authors.initials: BS
authors.lastname: Wilson
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats
chemical_list: D000089982:ADP-Ribosylation Factor 6; D002135:Calcium-Binding Proteins; D002966:Clathrin; C526966:Eps15 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D020727:ADP-Ribosylation Factors; C000715349:Arf6 protein, rat; D034281:Dynamins
keywords: Arf6; CIE; CME; Endocytosis; Eps15; FcεRI; Mast cell