VAP-B binds to Rab3GAP1 at the ER: its implication in nuclear envelope formation through the ER-Golgi intermediate compartment.
VAP-B binds to Rab3GAP1 at the ER: its implication in nuclear envelope formation through the ER-Golgi intermediate compartment.
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发表时间：
2014-10
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通讯作者：
Degejirihu Hantan;Yasunori Yamamoto;T. Sakisaka
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作者：
Degejirihu Hantan;Yasunori Yamamoto;T. Sakisaka
囊泡相关膜蛋白相关蛋白B(VAP-B)是一种位于内质网(ER)的尾锚式蛋白。VAP-B作为一种适配蛋白将靶蛋白募集到内质网，执行多种细胞功能，如脂质转运、膜运输、内质网应激等。最近研究表明，VAP-B调节核膜蛋白通过内质网高尔基体中间室(ERGIC)的转运。我们在这里证明了VAP-B通过Rab3GAP1的催化亚基Rab3GTPase激活蛋白1(Rab3GAP1)直接与Rab3GAP1结合，这是通过Rab3GAP1的酸性链(FFAT)样基序中的两个苯丙氨酸(FF)来实现的。Rab3GAP由两个亚基组成，催化亚基Rab3GAP1和非催化亚基Rab3GAP2。VAP-B即使在Rab3GAP1/2异源二聚体复合体中也能与Rab3GAP1结合。FFAT类基序的单一氨基酸取代降低了Rab3GAP1与VAP-B的结合活性。另一方面，FFAT样基序突变增加了Rab3GAP1与ERGIC标记蛋白ERGIC-53的结合活性。与Rab3GAP1类FFAT突变体相比，Rab3GAP1过表达对核膜形成的影响更大。这些结果表明，VAP-B与Rab3GAP1的结合参与了ERGIC对核膜形成的调控。
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.