Identification of multiple post-translational modifications in the porcine brain specific p25alpha.

Abstract:

:P25alpha is a protein normally expressed in oligodendrocytes and subcellular relocalization of p25alpha occurs in multiple system atrophy, Parkinson's disease and Lewy body dementia along with ectopic expression in neurons. Moreover, it accumulates in Lewy body inclusions with aggregated alpha-synuclein and is a potent stimulator of alpha-synuclein aggregation. P25alpha is a phosphoprotein and post-translational modifications (PTMs) may play a role in its disease-related abnormalities. To investigate the spectrum of PTMs on p25alpha we cloned porcine p25alpha and isolated the protein from porcine brain. Using several complementary tandem mass spectrometry techniques for peptide mass analysis and amino acid sequencing, a comprehensive analysis of the PTMs on porcine p25alpha was performed. It was found that porcine p25alpha is heavily modified with a variety of modifications: phosphorylation, di- and trimethylation, citrullination and a HexNAc group. The modifications are localized within p25alpha's unfolded terminal domains and suggest that their functional states are regulated. This comprehensive mapping of p25alpha's PTMs will form the basis for future functional studies and investigations of p25alpha's potential role as a biomarker.

journal_name

J Neurochem

authors

Kleinnijenhuis AJ,Hedegaard C,Lundvig D,Sundbye S,Issinger OG,Jensen ON,Jensen PH

doi

10.1111/j.1471-4159.2008.05437.x

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

925-33

issue

2

eissn

0022-3042

issn

1471-4159

pii

JNC5437

journal_volume

106

pub_type

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