Evidence map›Paper›PMID 41171761›Full record

ArticleCell reports2025

Phospho-proteome profiling in human neurons reveals targets of TBK1 in ALS/FTD-associated autophagy networks.

Julie Smeyers, Juan A Oses-Prieto, Lin Yadanar, Man Wang, Marci Iadarola, Serena Lu, Karen S Wang, Taylor H Watanabe, Jayanta Debnath, Alma L Burlingame and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Julie SmeyersInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Juan A Oses-PrietoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Lin YadanarInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Man WangInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Marci IadarolaInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Serena LuInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Karen S WangInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Taylor H WatanabeInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Jayanta DebnathHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Daniel A MordesInstitute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: daniel.mordes@ucsf.edu.

Funding

Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher · 2020 to 2026
$4.5M
Defining TBK1-associated autophagy networks in neuronsR01AG089849 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Daniel Adam Mordes · 2024 to 2026
$2.3M
NIA NIH HHS R01 AG089849NIGMS NIH HHS T32 GM136547
6 · The paper itself

Abstract

Loss-of-function variants in TBK1, encoding a protein kinase, are strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, how haploinsufficiency for TBK1 leads to age-related neurodegeneration remains unresolved. Here, we utilize sets of isogenic induced pluripotent stem cells (iPSCs) with loss of TBK1 or loss of optineurin (OPTN) for quantitative global proteomics and phospho-proteomics in both stem cells and excitatory neurons. We found that TBK1 sustains the abundance and phosphorylation of its interacting adapter proteins, AZI2/NAP1, TANK, and TBKBP1/SINTBAD. Moreover, TBK1 regulates the phosphorylation of endo-lysosomal proteins, such as GABARAPL2, the late-endosome GTPase RAB7A, and selective autophagy cargo receptor proteins-including novel phospho-sites in p62/SQSTM1-in neurons. Finally, we provide a census of the phospho-proteome in nascent human neurons for further studies. Overall, TBK1 serves as a point of convergence in ALS/FTD-linked endo-lysosomal networks that act in a cell-autonomous manner to maintain protein homeostasis in neurons.

Indexed as

Amyotrophic Lateral SclerosisAutophagyFrontotemporal DementiaNeuronsPhosphoproteinsProtein Serine-Threonine KinasesProteomeCell Cycle ProteinsHumansInduced Pluripotent Stem CellsMembrane Transport ProteinsPhosphorylationProteomicsTranscription Factor TFIIIACell Cycle ProteinsMembrane Transport ProteinsOPTN protein, humanPhosphoproteinsProtein Serine-Threonine KinasesProteomeTBK1 protein, humanTranscription Factor TFIIIAALSautophagyCP: Molecular biologyCP: NeurosciencedementiaiPSC disease modelingneurodegenerationOPTNphospho-proteomicsproteomicsTBK1

Identifiers

PMID41171761
PMCPMC12967247

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.