Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from Cytoskeleton
Nuclear shape modulates cell behavior and function, while aberrant nuclear morphologies correlate with pathological phenotype severity. Nevertheless, functions of specific nuclear morphological features and underlying molecular mechanisms remain poorly understood. Here, we investigate a nucleus-intr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2509 |
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| author | Sebastian Martewicz Camilla Luni Xi Zhu Meihua Cui Manli Hu Siqi Qu Damiano Buratto Guang Yang Eleonora Grespan Nicola Elvassore |
| author_facet | Sebastian Martewicz Camilla Luni Xi Zhu Meihua Cui Manli Hu Siqi Qu Damiano Buratto Guang Yang Eleonora Grespan Nicola Elvassore |
| author_sort | Sebastian Martewicz |
| collection | DOAJ |
| description | Nuclear shape modulates cell behavior and function, while aberrant nuclear morphologies correlate with pathological phenotype severity. Nevertheless, functions of specific nuclear morphological features and underlying molecular mechanisms remain poorly understood. Here, we investigate a nucleus-intrinsic mechanism driving nuclear lobulation and segmentation concurrent with granulocyte specification, independently from extracellular forces and cytosolic cytoskeleton contributions. Transcriptomic regulation of cholesterol biosynthesis is equally concurrent with nuclear remodeling. Its putative role as a regulatory element is supported by morphological aberrations observed upon pharmacological impairment of several enzymatic steps of the pathway, most prominently the sterol ∆14-reductase activity of laminB-receptor and protein prenylation. Thus, we support the hypothesis of a nuclear-intrinsic mechanism for nuclear shape control with the putative involvement of the recently discovered GGTase III complex. Such process could be independent from or complementary to the better studied cytoskeleton-based nuclear remodeling essential for cell migration in both physiological and pathological contexts such as immune system function and cancer metastasis. |
| first_indexed | 2024-03-10T14:43:02Z |
| format | Article |
| id | doaj.art-8e3b439265f448ca98736bad02430447 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:43:02Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8e3b439265f448ca98736bad024304472023-11-20T21:39:34ZengMDPI AGCells2073-44092020-11-01911250910.3390/cells9112509Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from CytoskeletonSebastian Martewicz0Camilla Luni1Xi Zhu2Meihua Cui3Manli Hu4Siqi Qu5Damiano Buratto6Guang Yang7Eleonora Grespan8Nicola Elvassore9Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaInstitute of Neuroscience, National Research Council, 35127 Padova, ItalyShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai 201210, ChinaNuclear shape modulates cell behavior and function, while aberrant nuclear morphologies correlate with pathological phenotype severity. Nevertheless, functions of specific nuclear morphological features and underlying molecular mechanisms remain poorly understood. Here, we investigate a nucleus-intrinsic mechanism driving nuclear lobulation and segmentation concurrent with granulocyte specification, independently from extracellular forces and cytosolic cytoskeleton contributions. Transcriptomic regulation of cholesterol biosynthesis is equally concurrent with nuclear remodeling. Its putative role as a regulatory element is supported by morphological aberrations observed upon pharmacological impairment of several enzymatic steps of the pathway, most prominently the sterol ∆14-reductase activity of laminB-receptor and protein prenylation. Thus, we support the hypothesis of a nuclear-intrinsic mechanism for nuclear shape control with the putative involvement of the recently discovered GGTase III complex. Such process could be independent from or complementary to the better studied cytoskeleton-based nuclear remodeling essential for cell migration in both physiological and pathological contexts such as immune system function and cancer metastasis.https://www.mdpi.com/2073-4409/9/11/2509nuclear morphologygranulocyte lobulationnuclear segmentationprenylationGGTase III |
| spellingShingle | Sebastian Martewicz Camilla Luni Xi Zhu Meihua Cui Manli Hu Siqi Qu Damiano Buratto Guang Yang Eleonora Grespan Nicola Elvassore Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from Cytoskeleton Cells nuclear morphology granulocyte lobulation nuclear segmentation prenylation GGTase III |
| title | Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from Cytoskeleton |
| title_full | Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from Cytoskeleton |
| title_fullStr | Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from Cytoskeleton |
| title_full_unstemmed | Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from Cytoskeleton |
| title_short | Nuclear Morphological Remodeling in Human Granulocytes Is Linked to Prenylation Independently from Cytoskeleton |
| title_sort | nuclear morphological remodeling in human granulocytes is linked to prenylation independently from cytoskeleton |
| topic | nuclear morphology granulocyte lobulation nuclear segmentation prenylation GGTase III |
| url | https://www.mdpi.com/2073-4409/9/11/2509 |
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