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

Fiore, Ana Paula Zen Petisco; Maity, Shuvadeep; Jeffery, Lauren; An, Disi; Rendleman, Justin; Iannitelli, Dylan; Choi, Hyungwon; Mazzoni, Esteban; Vogel, Christine

doi:10.1016/j.celrep.2024.113885

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2024

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Cited by 2 publications

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Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases

Kampmann

2024

Nat. Rev. Neurosci.

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Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases

Kampmann

2024

Nat. Rev. Neurosci.

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The landscape of cellular clearance systems across human tissues and cell types is shaped by tissue-specific proteome needs

Vinogradov,

Ravkaie,

Edri

et al. 2024

Preprint

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Protein clearance is fundamental to proteome health. In eukaryotes, it is carried by two highly conserved proteolytic systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP). Despite their pivotal role, the basal organization of the human protein clearance systems across tissues and cell types remains uncharacterized. Here, we interrogated this organization using diverse omics datasets. Relative to other protein-coding genes, UPS and ALP genes were more widely expressed, encoded more housekeeping proteins, and were more essential for growth, in accordance with their fundamental roles. Most of the UPS and ALP genes were nevertheless differentially expressed across tissues, and their tissue-specific upregulation was associated with tissue-specific functions, phenotypes, and disease susceptibility. The small subset of UPS and ALP genes that was stably expressed across tissues was more highly and widely expressed and more essential for growth than other UPS and ALP genes, suggesting that it acts as a core. Lastly, we compared protein clearance to other branches of the proteostasis network. Protein clearance and folding were closely coordinated across tissues, yet both were less pivotal than protein synthesis. Taken together, we propose that the proteostasis network is organized hierarchically and is tailored to the proteome needs. This organization could contribute to and illuminate tissue-selective phenotypes.

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

Cited by 2 publications

References 129 publications

Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases

Molecular and cellular mechanisms of selective vulnerability in neurodegenerative diseases

The landscape of cellular clearance systems across human tissues and cell types is shaped by tissue-specific proteome needs

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