Novel isoforms of tau that lack the microtubule-binding domain.
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.
Luo
Min-Hua
MH
Neurobiology Division, Shriver Center, Waltham, Massachusetts 02452, USA.
Tse
Sze-Wah
SW
Memmott
John
J
Andreadis
Athena
A
D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D005091:Exons / Q000235:genetics; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D016875:tau Proteins