Proteomics

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Phospho-proteome profiling in human induced pluripotent stem cells and derived human neurons reveals targets of TBK1 in ALS/FTD-1 associated autophagy networks


ABSTRACT: TBK1 (TANK-binding kinase 1) is a ubiquitously expressed IKK-related kinase implicated in diverse cellular processes, including interferon signaling, apoptosis, and autophagy. Loss-of-function variants in TBK1 are strongly associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the targets of TBK1 in neurons are unknown, and how haploinsufficiency for TBK1 leads to age-related neurodegeneration remains unresolved. Here, we utilized sets of isogenic induced pluripotent stem cells (iiPSCs) for unbiased, quantitative phospho-proteomics across tens of thousands of phospho-sites, normalized to protein abundance, in proliferating stem cells and induced excitatory neurons. We found that TBK1 primarily regulates the phosphorylation of selective autophagy proteins, particularly phospho-serine residues within cargo receptors, and endo-lysosomal pathways.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pluripotent Stem Cell

SUBMITTER: Juan Oses-Prieto  

LAB HEAD: Daniel Mordes

PROVIDER: PXD068150 | Pride | 2025-09-11

REPOSITORIES: Pride

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