title: Bap31 is an itinerant protein that moves between the peripheral endoplasmic reticulum (ER) and a juxtanuclear compartment related to ER-associated Degradation.
abstract: Certain endoplasmic reticulum (ER)-associated degradation (ERAD) substrates with transmembrane domains are segregated from other ER proteins and sorted into a juxtanuclear subcompartment, known as the ER quality control compartment. Bap31 is an ER protein with three transmembrane domains, and it is assumed to be a cargo receptor for ER export of some transmembrane proteins, especially those prone to ERAD. Here, we show that Bap31 is a component of the ER quality control compartment and that it moves between the peripheral ER and a juxtanuclear ER or ER-related compartment distinct from the conventional ER-Golgi intermediate compartment. The third and second transmembrane domains of Bap31 are principally responsible for the movement to and recycling from the juxtanuclear region, respectively. This cycling was blocked by depolymerization of microtubules and disruption of dynein-dynactin function. Overexpression of Sar1p and Arf1 mutants affected Bap31 cycling, suggesting that this cycling pathway is related to the conventional vesicular transport pathways.
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Wakana
authors.forename: Sawako
authors.initials: S
authors.lastname: Takai
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Katsuko
authors.initials: K
authors.lastname: Tani
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Peter
authors.initials: P
authors.lastname: Watson
authors.forename: David J
authors.initials: DJ
authors.lastname: Stephens
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hauri
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tagaya
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D020126:Brefeldin A / Q000494:pharmacology; D002451:Cell Compartmentation / Q000187:drug effects; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C091247:BCAP31 protein, human; C487709:DERL1 protein, human; D007546:Isoquinolines; C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D013449:Sulfonamides; D020126:Brefeldin A; D020823:ADP-Ribosylation Factor 1; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide