Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons
Summary: Amyotrophic lateral sclerosis damages proteostasis, affecting spinal and upper motor neurons earlier than a subset of cranial motor neurons. To aid disease understanding, we exposed induced cranial and spinal motor neurons (iCrMNs and iSpMNs) to proteotoxic stress, under which iCrMNs showed...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724002134 |
| _version_ | 1797267850483728384 |
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| author | Ana Paula Zen Petisco Fiore Shuvadeep Maity Lauren Jeffery Disi An Justin Rendleman Dylan Iannitelli Hyungwon Choi Esteban Mazzoni Christine Vogel |
| author_facet | Ana Paula Zen Petisco Fiore Shuvadeep Maity Lauren Jeffery Disi An Justin Rendleman Dylan Iannitelli Hyungwon Choi Esteban Mazzoni Christine Vogel |
| author_sort | Ana Paula Zen Petisco Fiore |
| collection | DOAJ |
| description | Summary: Amyotrophic lateral sclerosis damages proteostasis, affecting spinal and upper motor neurons earlier than a subset of cranial motor neurons. To aid disease understanding, we exposed induced cranial and spinal motor neurons (iCrMNs and iSpMNs) to proteotoxic stress, under which iCrMNs showed superior survival, quantifying the transcriptome and proteome for >8,200 genes at 0, 12, and 36 h. Two-thirds of the proteome showed cell-type differences. iSpMN-enriched proteins related to DNA/RNA metabolism, and iCrMN-enriched proteins acted in the endoplasmic reticulum (ER)/ER chaperone complex, tRNA aminoacylation, mitochondria, and the plasma/synaptic membrane, suggesting that iCrMNs expressed higher levels of proteins supporting proteostasis and neuronal function. When investigating the increased proteasome levels in iCrMNs, we showed that the activity of the 26S proteasome, but not of the 20S proteasome, was higher in iCrMNs than in iSpMNs, even after a stress-induced decrease. We identified Ublcp1 as an iCrMN-specific regulator of the nuclear 26S activity. |
| first_indexed | 2024-04-25T01:23:08Z |
| format | Article |
| id | doaj.art-ec67cb62c095414cb313530ab059cdee |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-25T01:23:08Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-ec67cb62c095414cb313530ab059cdee2024-03-09T09:24:53ZengElsevierCell Reports2211-12472024-03-01433113885Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neuronsAna Paula Zen Petisco Fiore0Shuvadeep Maity1Lauren Jeffery2Disi An3Justin Rendleman4Dylan Iannitelli5Hyungwon Choi6Esteban Mazzoni7Christine Vogel8New York University, Department of Biology, New York, NY 10003, USANew York University, Department of Biology, New York, NY 10003, USA; Department of Biological Sciences, Birla Institute of Technology and Science Pilani, Hyderabad Campus, Hyderabad, Telangana, IndiaNew York University, Department of Biology, New York, NY 10003, USANew York University, Department of Biology, New York, NY 10003, USANew York University, Department of Biology, New York, NY 10003, USANew York University, Department of Biology, New York, NY 10003, USADepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, SingaporeNew York University, Department of Biology, New York, NY 10003, USA; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USANew York University, Department of Biology, New York, NY 10003, USA; Corresponding authorSummary: Amyotrophic lateral sclerosis damages proteostasis, affecting spinal and upper motor neurons earlier than a subset of cranial motor neurons. To aid disease understanding, we exposed induced cranial and spinal motor neurons (iCrMNs and iSpMNs) to proteotoxic stress, under which iCrMNs showed superior survival, quantifying the transcriptome and proteome for >8,200 genes at 0, 12, and 36 h. Two-thirds of the proteome showed cell-type differences. iSpMN-enriched proteins related to DNA/RNA metabolism, and iCrMN-enriched proteins acted in the endoplasmic reticulum (ER)/ER chaperone complex, tRNA aminoacylation, mitochondria, and the plasma/synaptic membrane, suggesting that iCrMNs expressed higher levels of proteins supporting proteostasis and neuronal function. When investigating the increased proteasome levels in iCrMNs, we showed that the activity of the 26S proteasome, but not of the 20S proteasome, was higher in iCrMNs than in iSpMNs, even after a stress-induced decrease. We identified Ublcp1 as an iCrMN-specific regulator of the nuclear 26S activity.http://www.sciencedirect.com/science/article/pii/S2211124724002134motor neuronsamyotrophic lateral sclerosisUblcp1unfolded protein responseproteasome |
| spellingShingle | Ana Paula Zen Petisco Fiore Shuvadeep Maity Lauren Jeffery Disi An Justin Rendleman Dylan Iannitelli Hyungwon Choi Esteban Mazzoni Christine Vogel Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons Cell Reports motor neurons amyotrophic lateral sclerosis Ublcp1 unfolded protein response proteasome |
| title | Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons |
| title_full | Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons |
| title_fullStr | Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons |
| title_full_unstemmed | Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons |
| title_short | Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons |
| title_sort | identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons |
| topic | motor neurons amyotrophic lateral sclerosis Ublcp1 unfolded protein response proteasome |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724002134 |
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