Overexpression of full-length but not N-terminal truncated isoform of microtubule-associated protein (MAP) 1B accelerates apoptosis of cultured cortical neurons.
beta-amyloid (Abeta) is presumed to play a pathogenic role in Alzheimer's disease (AD). However, there is an imperfect correlation between Abeta deposition and neuronal loss or dementia. To clarify neuronal responses to Abeta, Abeta-induced gene expression in cultured cortical neurons was analyzed by differential display followed by Northern blotting. Here we report that nonaggregated or aggregated Abeta induced microtubule-associated protein 1B (MAP1B) mRNA, especially the alternative transcript containing exon 3U, before disruption of the cell membrane by Abeta. An alternative transcript containing exon 3U is translated into an N-terminal truncated shorter isoform of MAP1B. Transfection experiments reveal that overexpression of this isoform does not accelerate neurite outgrowth or apoptosis of cortical neurons. In contrast, overexpression of MAP1B fragments containing the N-terminal 126 amino acids promoted neurite outgrowth and neuronal apoptosis. These results suggest that Abeta does not induce deleterious full-length MAP1B directly, but overexpression of full-length MAP1B might act as an effector of cell death in neurodegenerative disorders related to cytoskeletal abnormalities.
Uchida
Yoko
Y
Gene Expression Research Group, Division of Neuroscience and Brain Function, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashiku, Tokyo 173-0015, Japan. uchiday@tmig.or.jp
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D016895:Culture Media, Serum-Free; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats
D016229:Amyloid beta-Peptides; D016895:Culture Media, Serum-Free; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; C075222:amyloid beta-protein (1-42); C085284:microtubule-associated protein 1B