The novel neurotrophin-regulated neuronal development-associated protein, NDAP, mediates apoptosis.
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.
Li
Hui Li
HL
Neuroscience Research Institute, Peking University, Key Laboratory of Neuroscience (PKU), Ministry of Education and Department of Neurobiology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China.
Li
Zhi
Z
Qin
Lu Ye
LY
Liu
Shuang
S
Lau
Lok Ting
LT
Han
Ji Sheng
JS
Yu
Albert Cheung Hoi
AC
D000217:Acyltransferases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D001923:Brain Chemistry; D002478:Cells, Cultured; D002540:Cerebral Cortex; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006624:Hippocampus; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014018:Tissue Distribution
D006133:Growth Substances; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D012333:RNA, Messenger; D000217:Acyltransferases; C081007:COOH-terminal signal transamidase