title: Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs.
abstract: In mammalian cells, the cortical endoplasmic reticulum (cER) is a network of tubules and cisterns that lie in close apposition to the plasma membrane (PM). We provide evidence that PM domains enriched in underlying cER function as trafficking hubs for insertion and removal of PM proteins in HEK 293 cells. By simultaneously visualizing cER and various transmembrane protein cargoes with total internal reflectance fluorescence microscopy, we demonstrate that the majority of exocytotic delivery events for a recycled membrane protein or for a membrane protein being delivered to the PM for the first time occur at regions enriched in cER. Likewise, we observed recurring clathrin clusters and functional endocytosis of PM proteins preferentially at the cER-enriched regions. Thus the cER network serves to organize the molecular machinery for both insertion and removal of cell surface proteins, highlighting a novel role for these unique cellular microdomains in membrane trafficking.
authors.affiliation: Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Fox
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Haberkorn
authors.forename: Aubrey V
authors.initials: AV
authors.lastname: Weigel
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Higgins
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Akin
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kennedy
authors.forename: Diego
authors.initials: D
authors.lastname: Krapf
authors.forename: Michael M
authors.initials: MM
authors.lastname: Tamkun
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D051665:Kv1.4 Potassium Channel / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D051669:Shab Potassium Channels / Q000378:metabolism
chemical_list: D002966:Clathrin; C496988:KCNB1 protein, human; D051665:Kv1.4 Potassium Channel; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D051669:Shab Potassium Channels