The Hob proteins: Putative, novel lipid transfer proteins at ER-PM contact sites.

Sarah D Neuman, Amy T Cavanagh, Arash Bashirullah
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Abstract

Nonvesicular transfer of lipids at membrane contact sites (MCS) has recently emerged as a critical process for cellular function. Lipid transfer proteins (LTPs) mediate this unique transport mechanism, and although several LTPs are known, the cellular complement of these proteins continues to expand. Our recent work has revealed the highly conserved but poorly characterized Hobbit/Hob proteins as novel, putative LTPs at endoplasmic reticulum-plasma membrane (ER-PM) contact sites. Using both S. cerevisiae and D. melanogaster model systems, we demonstrated that the Hob proteins localize to ER-PM contact sites via an N-terminal ER membrane anchor and conserved C-terminal sequences. These conserved C-terminal sequences bind to phosphoinositides (PIPs), and the distribution of PIPs is disrupted in hobbit mutant cells. Recently released structural models of the Hob proteins exhibit remarkable similarity to other bona fide LTPs, like VPS13A and ATG2, that function at MCS. Hobbit is required for viability in Drosophila, suggesting that the Hob proteins are essential genes that may mediate lipid transfer at MCS.

Abstract Image

Hob蛋白:在ER-PM接触位点推测的新型脂质转移蛋白。
脂质在膜接触位点的非囊泡转移(MCS)最近已成为细胞功能的关键过程。脂质转移蛋白(LTP)介导这种独特的转运机制,尽管已知几种LTP,但这些蛋白的细胞补体仍在继续扩增。我们最近的工作揭示了高度保守但特征较差的Hobit/Hob蛋白是内质网质膜(ER-PM)接触位点的新的、假定的LTP。使用酿酒酵母和黑腹果蝇模型系统,我们证明了Hob蛋白通过N端ER膜锚和保守的C端序列定位在ER-PM接触位点。这些保守的C末端序列与磷酸肌醇(PIP)结合,PIP在霍比特突变细胞中的分布被破坏。最近发布的Hob蛋白的结构模型与其他真正的LTP(如VPS13A和ATG2)表现出显著的相似性,这些LTP在MCS下发挥作用。Hobit是果蝇生存能力所必需的,这表明Hob蛋白是可能在MCS下介导脂质转移的重要基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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