The novel neurotrophin-regulated neuronal development-associated protein, NDAP, mediates apoptosis

Hui Li Li, Zhi Li, Lu Ye Qin, Shuang Liu, Lok Ting Lau, Ji Sheng Han, Albert Cheung Hoi Yu

Research output: Contribution to journalArticle

Abstract

We identified a novel gene and named it, "neuronal development-associated protein (NDAP)". We detected NDAP mRNA presence in most tissues including the brain where it was present in the area from the external granular layer to the multiform layer in the cerebral cortex, and in CA1, CA2, CA3 and the dentate gyrus in the hippocampus. Its expression increased transiently in primary cultures of 2-4 day neurons and 1-2 week astrocytes and was significantly reduced in older cultures. Treatment by the neurotrophin, NT-3, significantly attenuated the decline of NDAP in neurons from days 2 to 10, whereas growth factors such as GDNF and insulin, and high potassium levels did not. To elucidate the effects of neurotrophins, we treated day 5 neurons with NT-3, BDNF or NGF for 48 h. NT-3 and BDNF both inhibited downregulation of NDAP mRNA levels but NGF slightly enhanced the already present downregulation; this effect of NGF was significant when examined in day 3 neurons. To investigate the potential function of NDAP, we over-expressed an NDAP-EGFP fusion protein in 4-week-old astrocytes. The newly expressed NDAP gradually aggregated into membrane-bound structures and eventually led to cell death through apoptosis by 24 h. Significant levels of cell death were also observed in NDAP-EGFP transfected HEK293 cells. Thus maintenance of high NDAP levels may cause apoptosis. The different regulations of NDAP expression by neurotrophins indicate that the expression of NDAP might be a checkpoint for apoptosis during neuronal development.

Original languageEnglish (US)
Pages (from-to)1723-1728
Number of pages6
JournalFEBS Letters
Volume580
Issue number7
DOIs
StatePublished - Mar 20 2006

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Keywords

  • Cell death
  • NT-3
  • Neuronal development
  • Neurotrophins
  • Over-expression

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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