title: Role of Sec24 isoforms in selective export of membrane proteins from the endoplasmic reticulum.
abstract: Sec24 of the COPII (coat protein complex II) vesicle coat mediates the selective export of membrane proteins from the endoplasmic reticulum (ER) in yeast. Human cells express four Sec24 isoforms, but their role is unknown. Here, we report the differential effects of Sec24 isoform-specific silencing on the transport of the membrane reporter protein ERGIC-53 (ER-Golgi intermediate compartment-53) carrying the cytosolic ER export signals di-phenylalanine, di-tyrosine, di-leucine, di-isoleucine, di-valine or terminal valine. Knockdown of single Sec24 isoforms showed dependence of di-leucine-mediated transport on Sec24A, but transport mediated by the other signals was not affected. By contrast, double knockdown of Sec24A with one of the other three Sec24 isoforms impaired all aromatic/hydrophobic signal-dependent transport. Double knockdown of Sec24B/C or Sec24B/D preferentially affected di-leucine-mediated transport, whereas knockdown of Sec24C/D affected di-isoleucine- and valine-mediated transport. The isoform-selective transport correlated with binding preferences of the signals for the corresponding isoforms in vitro. Thus, human Sec24 isoforms expand the repertoire of cargo for signal-mediated ER export, but are in part functionally redundant.
authors.affiliation: Department of Pharmacology and Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Wendeler
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Paccaud
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hauri
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D034741:RNA, Small Interfering; C530638:SEC24A protein, human; C530639:SEC24B protein, human; C530640:SEC24C protein, human; D033921:Vesicular Transport Proteins