Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons.

Autor:	Fiore APZP; New York University, Department of Biology, New York, NY 10003, USA., Maity S; New 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, India., Jeffery L; New York University, Department of Biology, New York, NY 10003, USA., An D; New York University, Department of Biology, New York, NY 10003, USA., Rendleman J; New York University, Department of Biology, New York, NY 10003, USA., Iannitelli D; New York University, Department of Biology, New York, NY 10003, USA., Choi H; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore., Mazzoni E; New York University, Department of Biology, New York, NY 10003, USA; Department of Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA., Vogel C; New York University, Department of Biology, New York, NY 10003, USA. Electronic address: cvogel@nyu.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 Mar 26; Vol. 43 (3), pp. 113885. Date of Electronic Publication: 2024 Mar 07.
DOI:	10.1016/j.celrep.2024.113885
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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