Novel Isoforms of Tau that lack the microtubule-binding domain

University of Massachusetts Amherst, Amherst Center, Massachusetts, United States
Journal of Neurochemistry (Impact Factor: 4.28). 08/2004; 90(2):340-51. DOI: 10.1111/j.1471-4159.2004.02508.x
Source: PubMed


Tau is a microtubule-associated protein (MAP) whose transcript undergoes complex regulated splicing in the mammalian nervous system. Our previous work with exon 6 established that tau shows a unique expression pattern and splicing regulation profile, and that it utilizes alternative splice sites in several human tissues. The mRNAs from these splicing events, if translated, would result in truncated tau variants that lack the microtubule-binding domain. In this study, we demonstrate that at least one of these tau variants is present as a stable protein in several tissues. The novel isoform shows a localization distinct from that of canonical tau in SH-SY5Y neuroblastoma cells which stably overexpress it. In both normal and Alzheimer's hippocampus, the novel isoform is found in dentate gyrus granular cells and CA1/CA3 pyramidal cells. However, it does not co-localize with canonical tau but, rather, partly co-localizes with MAP2.

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Available from: Sze-Wah Tse, Oct 08, 2014
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    • "All six possible product combinations of the 2/3/10 splicing events have been observed (figure 3B), indicating that separate factors govern their splicing (Andreadis, 2011). Alternative splicing of hinge-region exon 6 gives rise to Tau variants that lack the domain responsible of microtubule binding, and is mentioned that alters Tau function (Andreadis, 2011; Luo et al., 2004). Saitohin (STH), an intronless gene encoding an open reading frame of 128 amino acids, is located in the intron between exons 9 and 10 of the human Tau gene (Wang et al., 2011). "
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    • "The amino acid numbering used for the recombinant tau proteins (Fig. 1) is based on the largest adult human isoform (ht40; 441 amino acids) in the central nervous system. Fulllength wild-type ht40 (WT tau) and the non-canonical N-terminal 6D isoform of tau were generated from the previously described pT7c plasmid cDNAs (LaPointe et al., 2009; Luo et al., 2004). Site-directed mutagenesis (Stratagene, QuickChange II Kit, 200524) was used to create point mutations in tau constructs. "
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