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AMPylation profiling during neuronal differentiation reveals extensive variation on lysosomal proteins

ABSTRACT: Protein AMPylation is a prevalent posttranslational modification with an emerging role in neurodevelopment and neurodegeneration. Although in metazoans the two highly conserved protein AMP-transferases together with diverse group of AMPylated proteins have been identified using chemical proteomics and biochemical techniques the function of this modification remains largely unknown. Particularly problematic is a localisation of thus far identified AMPylated proteins and putative AMP-transferases. Here, we uncover protein AMPylation as a novel lysosomal protein posttranslational modification characteristic for differentiating neurons. The AMPylated soluble form of exonuclease PLD3 localised in lysosomes shows dramatic increase during the differentiation of neuronal cell lineages. Similar AMPylation pattern has been observed for a lysosomal acid phosphatase ACP2. Our discovery was enabled by combination of chemical proteomics and novel gel-based separation technique of modified and non-modified proteins. Together, our findings expose further the connection between the protein AMPylation and neurodevelopment and reveal a novel lysosomal posttranslational modification.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

SUBMITTER: Tobias Becker

LAB HEAD: Dr. Pavel Kielkowski

PROVIDER: PXD023873 | Pride | 2021-12-01

REPOSITORIES: Pride

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			Action	DRS
	20200316_TB10_24_C1.raw	Raw
	20200316_TB10_24_C2.raw	Raw
	20200316_TB10_24_C3.raw	Raw
	20200316_TB10_24_C4.raw	Raw
	20200316_TB10_24_P1.raw	Raw

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