The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1,Molecular Cell, 2 Dec 2019
The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1
Guangyan Miao, Yujie Zhang,Di Chen, HongZhang
Summary
TMEM39A, encoding an ER-localized transmembrane protein, is a susceptibility locus for multiple autoimmune diseases. The molecular function ofTMEM39Aremains completely unknown. Here we demonstrated thatTMEM39A, also calledSUSR2, modulates autophagy activity by regulating the spatial distribution and levels of PtdIns(4)P. Depletion ofSUSR2elevates late endosomal/lysosomal PtdIns(4)P levels, facilitating recruitment of the HOPS complex to promote assembly of the SNARE complex for autophagosome maturation.SUSR2knockdown also increases the degradative capability of lysosomes. Mechanistically, SUSR2 interacts with the ER-localized PtdIns(4)P phosphatase SAC1 and also the COPII SEC23/SEC24 subunits to promote the ER-to-Golgi transport of SAC1. Retention of SAC1 on the ER inSUSR2knockdown cells increases the level of PtdIns(3)P produced by the VPS34 complex, promoting autophagosome formation. Our study reveals that TMEM39A/SUSR2 acts as an adaptor protein for efficient export of SAC1 from the ER and provides insights into the pathogenesis of diseases associated withTMEM39Amutations.
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The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1,Molecular Cell, 2 Dec 2019
Molecular Cell, 2 December, 2019，DOI：https://doi.org/10.1016/j.molcel.2019.10.035
The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1
Guangyan Miao, Yujie Zhang,Di Chen, HongZhang
Summary
TMEM39A, encoding an ER-localized transmembrane protein, is a susceptibility locus for multiple autoimmune diseases. The molecular function ofTMEM39Aremains completely unknown. Here we demonstrated thatTMEM39A, also calledSUSR2, modulates autophagy activity by regulating the spatial distribution and levels of PtdIns(4)P. Depletion ofSUSR2elevates late endosomal/lysosomal PtdIns(4)P levels, facilitating recruitment of the HOPS complex to promote assembly of the SNARE complex for autophagosome maturation.SUSR2knockdown also increases the degradative capability of lysosomes. Mechanistically, SUSR2 interacts with the ER-localized PtdIns(4)P phosphatase SAC1 and also the COPII SEC23/SEC24 subunits to promote the ER-to-Golgi transport of SAC1. Retention of SAC1 on the ER inSUSR2knockdown cells increases the level of PtdIns(3)P produced by the VPS34 complex, promoting autophagosome formation. Our study reveals that TMEM39A/SUSR2 acts as an adaptor protein for efficient export of SAC1 from the ER and provides insights into the pathogenesis of diseases associated withTMEM39Amutations.
文章链接：https://www.sciencedirect.com/science/article/pii/S1097276519308135?via%3Dihub
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