Expression of α-subunit of α-glucosidase II in adult mouse brain regions and selected organs

Antje Anji, Hayley Miller, Chandrasekar Raman, Mathew Phillips, Gary Ciment, Meena Kumari

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

α-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of α (GIIα) and β (GIIβ) subunits. The catalytic GIIα subunit, with the help of mannose 6-phosphate receptor homology domain of GIIβ, sequentially hydrolyzes two α1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. The soluble GIIα subunit is retained in the ER through its interaction with the HDEL-containing GIIβ subunit. N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. Despite the widespread use of GIIα inhibitory drugs and the role of GIIα in brain function, little is known about its expression in brain and other tissues. Here, we report generation of a highly specific chicken antibody to the GIIα subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. By using this antibody, we showed that the GIIα protein is highly expressed in testis, kidney, and lung, with the lowest amount in heart. GIIα polypeptide levels in whole brain were comparable to those in spleen. However, a higher expression of GIIα protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins.

Original languageEnglish (US)
Pages (from-to)82-93
Number of pages12
JournalJournal of Neuroscience Research
Volume93
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Cerebral cortex
  • Chicken antibody
  • GIIα
  • Immunoprecipitation
  • Mouse
  • N-glycosylation
  • Protein folding
  • Western blot analysis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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