Quantitative phosphoproteomics reveals that nestin is a downstream target of dual leucine zipper kinase during retinoic acid-induced neuronal differentiation of Neuro-2a cells

BMC Molecular and Cell Biology, Год журнала: 2025, Номер 26(1)

Опубликована: Март 26, 2025

Dual leucine zipper kinase (DLK) is critical for neurite outgrowth in the developing nervous system and during nerve regeneration, but underlying mechanisms remain largely unknown. To address this issue, we generated stable shRNA-mediated DLK-depleted Neuro-2a cell lines analyzed their phosphoproteome after induction of neuronal differentiation by retinoic acid (RA). Here, report identification 32 phosphopeptides that exhibited significant differences relative abundance between control cells. Two most downregulated identified DLK depletion were derived from nestin, a type VI intermediate filament (IF) protein typically expressed neural progenitor The reduced these response to knockdown was validated using parallel reaction monitoring (PRM)-based quantitative proteomics paired with concomitant reduction nestin mRNA expression, indicating decrease phosphorylation due total cells compared This DLK-mediated regulation expression had no apparent effect on formation because alone not sufficient impair RA-induced extension parental cells, overexpression failed rescue defect observed Together, results demonstrate novel downstream target signaling mediator its ability promote differentiation.

Язык: Английский

Flipping a switch on BRD4: How to control the do-it-all

Molecular Cell, Год журнала: 2024, Номер 84(22), С. 4257 - 4259

Опубликована: Ноя. 1, 2024

Язык: Английский