A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis
The integral membrane protein Apq12 is an important nuclear envelope (NE)/endoplasmic reticulum (ER) modulator that cooperates with the nuclear pore complex (NPC) biogenesis factors Brl1 and Brr6. How Apq12 executes these functions is unknown. Here, we identified a short amphipathic α-helix (AαH) in...
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| Format: | Article |
| Language: | English |
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The Royal Society
2021-11-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.210250 |
| _version_ | 1797821759582371840 |
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| author | Wanlu Zhang Azqa Khan Jlenia Vitale Annett Neuner Kerstin Rink Christian Lüchtenborg Britta Brügger Thomas H. Söllner Elmar Schiebel |
| author_facet | Wanlu Zhang Azqa Khan Jlenia Vitale Annett Neuner Kerstin Rink Christian Lüchtenborg Britta Brügger Thomas H. Söllner Elmar Schiebel |
| author_sort | Wanlu Zhang |
| collection | DOAJ |
| description | The integral membrane protein Apq12 is an important nuclear envelope (NE)/endoplasmic reticulum (ER) modulator that cooperates with the nuclear pore complex (NPC) biogenesis factors Brl1 and Brr6. How Apq12 executes these functions is unknown. Here, we identified a short amphipathic α-helix (AαH) in Apq12 that links the two transmembrane domains in the perinuclear space and has liposome-binding properties. Cells expressing an APQ12 (apq12-ah) version in which AαH is disrupted show NPC biogenesis and NE integrity defects, without impacting Apq12-ah topology or NE/ER localization. Overexpression of APQ12 but not apq12-ah triggers striking over-proliferation of the outer nuclear membrane (ONM)/ER and promotes accumulation of phosphatidic acid (PA) at the NE. Apq12 and Apq12-ah both associate with NPC biogenesis intermediates and removal of AαH increases both Brl1 levels and the interaction between Brl1 and Brr6. We conclude that the short amphipathic α-helix of Apq12 regulates the function of Brl1 and Brr6 and promotes PA accumulation at the NE possibly during NPC biogenesis. |
| first_indexed | 2024-03-13T09:57:32Z |
| format | Article |
| id | doaj.art-49f2b3970e5e42359e25debff6fe7f98 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-03-13T09:57:32Z |
| publishDate | 2021-11-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-49f2b3970e5e42359e25debff6fe7f982023-05-23T13:48:33ZengThe Royal SocietyOpen Biology2046-24412021-11-01111110.1098/rsob.210250A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesisWanlu Zhang0Azqa Khan1Jlenia Vitale2Annett Neuner3Kerstin Rink4Christian Lüchtenborg5Britta Brügger6Thomas H. Söllner7Elmar Schiebel8Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyZentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyZentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyZentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyBiochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, GermanyBiochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, GermanyBiochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, GermanyBiochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, GermanyZentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Allianz, Im Neuenheimer Feld 282, 69120 Heidelberg, GermanyThe integral membrane protein Apq12 is an important nuclear envelope (NE)/endoplasmic reticulum (ER) modulator that cooperates with the nuclear pore complex (NPC) biogenesis factors Brl1 and Brr6. How Apq12 executes these functions is unknown. Here, we identified a short amphipathic α-helix (AαH) in Apq12 that links the two transmembrane domains in the perinuclear space and has liposome-binding properties. Cells expressing an APQ12 (apq12-ah) version in which AαH is disrupted show NPC biogenesis and NE integrity defects, without impacting Apq12-ah topology or NE/ER localization. Overexpression of APQ12 but not apq12-ah triggers striking over-proliferation of the outer nuclear membrane (ONM)/ER and promotes accumulation of phosphatidic acid (PA) at the NE. Apq12 and Apq12-ah both associate with NPC biogenesis intermediates and removal of AαH increases both Brl1 levels and the interaction between Brl1 and Brr6. We conclude that the short amphipathic α-helix of Apq12 regulates the function of Brl1 and Brr6 and promotes PA accumulation at the NE possibly during NPC biogenesis.https://royalsocietypublishing.org/doi/10.1098/rsob.210250APQ12BRR6nuclear pore complexnuclear envelopeBRL1nuclear pore complex biogenesis |
| spellingShingle | Wanlu Zhang Azqa Khan Jlenia Vitale Annett Neuner Kerstin Rink Christian Lüchtenborg Britta Brügger Thomas H. Söllner Elmar Schiebel A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis Open Biology APQ12 BRR6 nuclear pore complex nuclear envelope BRL1 nuclear pore complex biogenesis |
| title | A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis |
| title_full | A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis |
| title_fullStr | A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis |
| title_full_unstemmed | A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis |
| title_short | A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis |
| title_sort | short perinuclear amphipathic α helix in apq12 promotes nuclear pore complex biogenesis |
| topic | APQ12 BRR6 nuclear pore complex nuclear envelope BRL1 nuclear pore complex biogenesis |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.210250 |
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