Constitutive expression and cytoplasmic compartmentalization of ATM protein in differentiated human neuron-like SH-SY5Y cells

Jessica K. Boehrs, Jinghua He, Marie Jo Halaby, Da Qing Yang

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Ataxia telangiectasia (A-T) is an autosomal, recessive disorder mainly characterized by neuronal degeneration. However, the reason for neuronal degeneration in A-T patients is still unclear. ATM (A-T, mutated), the gene mutated in A-T, encodes a 370-kDa protein kinase. We measured the levels of the ATM protein found in differentiated neuron-like rat PC12 cells and differentiated neuron-like human SH-SY5Y cells. We found that, in rat PC12 cells, ATM levels decreased dramatically after differentiation, which is consistent with previous results observed in differentiated mouse neural progenitor cells. In contrast, the levels of ATM were similar before and after differentiation in human SH-SY5Y cells. Using an indirect immunofluorescence assay, we showed that ATM translocates from the nucleus to the cytoplasm in differentiated human SH-SY5Y cells. The translocation of ATM was further verified by subcellular fractionation experiments. The constitutive expression and cytoplasmic translocation of ATM in differentiated SH-SY5Y cells suggest that ATM is important for maintaining the regular function of human neuronal cells. Our results further demonstrated that, in response to insulin, ATM protects differentiated neuron-like SH-SY5Y cells from serum starvation-induced apoptosis. These data provide the first evidence that cytoplasmic ATM promotes survival of human neuronal cells in an insulin-dependent manner.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalJournal of Neurochemistry
Volume100
Issue number2
DOIs
StatePublished - Jan 2007

Keywords

  • Ataxia-telangiectasia mutated
  • Neuronal differentiation and survival
  • Protein expression
  • Protein translocation

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