title: VAP-B binds to Rab3GAP1 at the ER: its implication in nuclear envelope formation through the ER-Golgi intermediate compartment.
abstract: The vesicle-associated membrane protein-associated protein B (VAP-B) is a tail-anchored protein in the endoplasmic reticulum (ER). VAP-B functions as an adaptor protein to recruit target proteins to the ER and execute various cellular functions, lipid transport, membrane traffic, ER stress etc. Recently, VAP-B has been shown to regulate the nuclear envelope protein transport through the ER-Golgi intermediate compartment (ERGIC). We showed here that VAP-B directly binds to Rab3 GTPase activating protein 1 (Rab3GAP1), the catalytic subunit of Rab3GAP, through the two phenylalanines (FF) in an acidic tract (FFAT)-like motif of Rab3GAP1. Rab3GAP consists of two subunits, the catalytic subunit Rab3GAP1 and the non-catalytic subunit Rab3GAP2. VAP-B binds to Rab3GAP1 even in the Rab3GAP1/2 heterodimer complex. A single amino acid substitution of the FFAT-like motif reduces the binding activity of Rab3GAP1 to VAP-B. On the other hand, the FFAT-like motif mutation increases the binding activity of Rab3GAP1 to ERGIC-53, the ERGIC marker protein. Overexpression of Rab3GAP1 affects nuclear envelope formation more potently than that of Rab3GAP1 FFAT-like motif mutant. These results suggest that the binding of VAP-B to Rab3GAP1 is implicated in the regulation of nuclear envelope formation through ERGIC.
authors.affiliation: Division of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Degejirihu
authors.initials: D
authors.lastname: Hantan
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sakisaka
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009685:Nuclear Envelope / Q000502:physiology*; D010649:Phenylalanine; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport; D051381:Rats; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D010649:Phenylalanine; C580955:RAB3GAP1 protein, human; D020692:rab3 GTP-Binding Proteins
keywords: ERGIC; Nuclear envelope; Rab3GAP; VAP-B