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Changes in synapsin 1 phosphorylation and tubulin acetylation in mice deficient in protein L‐isoaspartyl methyltransferase
Author(s) -
Qin Zhenxia,
Aswad Dana W.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.553.11
Subject(s) - synapsin , synapsin i , phosphorylation , tubulin , acetylation , in vivo , stathmin , kinase , neurotransmission , blot , biology , medicine , microtubule , gap 43 protein , endocrinology , chemistry , microbiology and biotechnology , biochemistry , receptor , immunology , synaptic vesicle , immunohistochemistry , gene , vesicle , membrane
Protein L‐isoaspartyl methyltransferase (PIMT) repairs damaged proteins that contain abnormal isoaspartyl (isoAsp) peptide bonds. PIMT knockout (KO) mice accumulate high levels of isoAsp damage in the brain and succumb to fatal epileptic seizures at 28–60 days after birth. Synapsin 1 and tubulin are major endogenous substrates for PIMT in brain, which could help explain the abnormal synaptic transmission and disorganized microtubules seen in the KO mice. To evaluate the effect of PIMT deficiency on the function of these proteins in vivo , we used Western blotting with modification‐specific antibodies to assess the state of phosphorylation of synapsin 1 and acetylation of tubulin. In female mice, phosphorylation of synapsin 1 at the Ser‐9 (protein kinase A) site was increased 145% in KO versus WT (wild type) mice. In males the increase was 22%. There was no change in phosphorylation at the Ser‐603 (CaM kinase II) site in either male or female mice. Acetylation of α‐tubulin at Lys‐40 was decreased approximately 28% in both male and female KO mice. These results show that isoAsp accumulations in synapsin 1 and tubulin are associated with functional changes in these proteins in vivo . We propose that these changes contribute to the aberrant neurotransmission and abnormal microtubule organization caused by PIMT deficiency.