title: Na,K-ATPase transport from endoplasmic reticulum to Golgi requires the Golgi spectrin-ankyrin G119 skeleton in Madin Darby canine kidney cells.
abstract: Spectrin (betaISigma*) and ankyrin (AnkG119) associate with Golgi membranes and the dynactin complex, but their role in vesicle trafficking remains uncertain. We find that the actin-binding domain and membrane-association domain 1 (MAD1) of betaI spectrin together form a constitutive Golgi targeting signal in transfected MDCK cells. Expression of this signal in transfected cells disrupts the endogenous Golgi spectrin skeleton and blocks transport of alpha- and beta-Na,K-ATPase and vesicular stomatitis virus-G protein from the endoplasmic reticulum (ER) but does not disrupt the formation of Golgi stacks, the distribution of beta-COP, or the transport and surface display of E-cadherin. The Golgi spectrin skeleton is thus required for the transport of a subset of membrane proteins from the ER to the Golgi. We postulate that together with polyfunctional adapter proteins such as AnkG119, Golgi spectrin forms a docking complex that acts prior to the cis-Golgi, presumably with vesicular-tubular clusters (VTCs or ERGIC), to sequester specific membrane proteins into vesicles transiting between the ER and Golgi, and subsequently (probably involving other isoforms of spectrin and ankyrin) to mediate cargo transport within the Golgi and to other membrane compartments. We hypothesize that this vesicular spectrin-ankyrin adapter-protein trafficking (or tethering) system (SAATS) mediates the capture and transport of many membrane proteins and acts in conjunction with vesicle-targeting molecules to effect the efficient transport of cargo proteins.
authors.affiliation: Department of Pediatrics, Yale University, New Haven, CT 06520, USA. prasad.devarajan@yale.edu
authors.forename: P
authors.initials: P
authors.lastname: Devarajan
authors.forename: P R
authors.initials: PR
authors.lastname: Stabach
authors.forename: M A
authors.initials: MA
authors.lastname: De Matteis
authors.forename: J S
authors.initials: JS
authors.lastname: Morrow
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006056:Golgi Apparatus / Q000201:enzymology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013049:Spectrin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D017487:Ankyrins; D021382:Protein Sorting Signals; D013049:Spectrin; D000254:Sodium-Potassium-Exchanging ATPase