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16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis
The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered c...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693007/ https://www.ncbi.nlm.nih.gov/pubmed/34984324 http://dx.doi.org/10.1016/j.isci.2021.103551 |
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author | Tomasello, Danielle L. Kim, Jiyoon L. Khodour, Yara McCammon, Jasmine M. Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H. Sive, Hazel |
author_facet | Tomasello, Danielle L. Kim, Jiyoon L. Khodour, Yara McCammon, Jasmine M. Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H. Sive, Hazel |
author_sort | Tomasello, Danielle L. |
collection | PubMed |
description | The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism. |
format | Online Article Text |
id | pubmed-8693007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-86930072022-01-03 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis Tomasello, Danielle L. Kim, Jiyoon L. Khodour, Yara McCammon, Jasmine M. Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H. Sive, Hazel iScience Article The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism. Elsevier 2021-12-02 /pmc/articles/PMC8693007/ /pubmed/34984324 http://dx.doi.org/10.1016/j.isci.2021.103551 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Tomasello, Danielle L. Kim, Jiyoon L. Khodour, Yara McCammon, Jasmine M. Mitalipova, Maya Jaenisch, Rudolf Futerman, Anthony H. Sive, Hazel 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
title | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
title_full | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
title_fullStr | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
title_full_unstemmed | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
title_short | 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis |
title_sort | 16pdel lipid changes in ipsc-derived neurons and function of fam57b in lipid metabolism and synaptogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8693007/ https://www.ncbi.nlm.nih.gov/pubmed/34984324 http://dx.doi.org/10.1016/j.isci.2021.103551 |
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