Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1.
Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism: Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1.
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DOI：
10.1016/j.bbrc.2011.08.106
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发表时间：
2011-09-30
影响因子：
3.1
通讯作者：
Roach, Peter J.
中科院分区：
文献类型：
--
作者：
Jiang, Sixin;Wells, Clark D.;Roach, Peter J.
糖原是葡萄糖的分支聚合物，在许多组织和细胞类型中充当细胞内碳和能量储备。其降解的一个重要途径是在自噬样过程中转运至溶酶体。有人提出，淀粉结合域蛋白1（Stbd1）可能参与这一机制，通过锚定糖原细胞内膜。此外，Stbd 1已被报道与已知的自噬蛋白GABARAPL 1相互作用，GABARAPL 1是Atg 8家族的成员。在这里，我们证实了这种相互作用，并通过细胞提取物的免疫共沉淀和细胞中共定位（免疫荧光显微镜证明）来判断，确定了Stbd 1中GABARAPL 1结合所必需的Atg 8相互作用基序（AIM）。Stbd 1 200 HEEWEMV 206的AIM序列位于分子的预测无序区域内，并符合货物特异性蛋白质（如p62和Nix）中其他AIM序列的共有序列。AIM的突变，包括W203或V206的单点突变，消除了Stbd 1与过表达和内源性GABARAPL 1的共定位。因此，Stbd1可能作为一种新的货物结合蛋白，在自噬途径中将糖原递送到溶酶体，该途径可称为“糖噬”。
Glycogen, a branched polymer of glucose, acts as an intracellular carbon and energy reserve in many tissues and cell types. An important pathway for its degradation is by transport to lysosomes in an autophagy-like process. It has been proposed that starch-binding domain-containing protein 1 (Stbd1) may participate in this mechanism by anchoring glycogen to intracellular membranes. In addition, Stbd1 has been reported to interact with a known autophagy protein, GABARAPL1, a member of the Atg8 family. Here, we confirm this interaction and identify an Atg8 interacting motif (AIM) in Stbd1 necessary for GABARAPL1 binding as judged by co-immunoprecipitation from cell extracts and co-localization in cells as evidenced by immunofluorescence microscopy. The AIM sequence of Stbd1 200HEEWEMV206 lies within a predicted disordered region of the molecule and fits the consensus of other AIM sequences in cargo-specifying proteins such as p62 and Nix. Mutation of the AIM, including single point mutations of either W203 or V206, eliminated the co-localization of Stbd1 with both over-expressed and endogenous GABARAPL1. Stbd1 may therefore function as a novel cargo binding protein that delivers glycogen to lysosomes in an autophagic pathway that could be termed “glycophagy”.
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影响因子：
6.8
作者：
Dunker, A. Keith;Silman, Israel;Sussman, Joel L.
通讯作者：
Sussman, Joel L.
影响因子：
16
作者：
Kirkin, Vladimir;Lamark, Trond;Johansen, Terje
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影响因子：
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影响因子：
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作者：
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通讯作者：
BRADFORD, MM