Overexpression of full-length but not N-terminal truncated isoform of microtubule-associated protein (MAP) 1B accelerates apoptosis of cultured cortical neurons

Abstract

β-amyloid (Aβ) is presumed to play a pathogenic role in Alzheimer's disease (AD). However, there is an imperfect correlation between Aβ deposition and neuronal loss or dementia. To clarify neuronal responses to Aβ, Aβ-induced gene expression in cultured cortical neurons was analyzed by differential display followed by Northern blotting. Here we report that nonaggregated or aggregated Aβ induced microtubule-associated protein 1B (MAP1B) mRNA, especially the alternative transcript containing exon 3U, before disruption of the cell membrane by Aβ. 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 Aβ 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.