Primary structure of high molecular weight tau present in the peripheral nervous system.
The tau proteins are a family of brain microtubule binding proteins that are required during axonal outgrowth and are found in neurofibrillary tangles in Alzheimer disease. A protein of higher molecular weight, immunologically related to tau, is expressed in the adult peripheral system and in cultured neuronal cell lines of neural crest origin. The predicted amino acid sequence of the high molecular weight tau from N115 cells has been determined from the sequence of its 2340-base-pair cDNA. High molecular weight tau contains an open reading frame encoding 733 amino acid residues. It contains sequences homologous to those present in the N-, middle, and C-terminal domains of adult brain tau proteins, including four homologous repeats, which are the tubulin binding sites, and an amino acid stretch, which is present only in the N-terminal domain of the mature brain variants. The middle region contains a previously unidentified nonhomologous stretch of 237 amino acid residues as well as a domain of 66 residues homologous to exon 6 of the bovine gene that is absent in all bovine, rat, and mouse tau cDNAs sequenced so far. A cDNA probe specific to the nonhomologous tau insert hybridizes to the 8- to 9-kilobase tau mRNA in N115 cells but not to the 6-kilobase tau mRNA in brain. Probes for the domains common to brain tau isoforms hybridize to both messages. The sequence of high molecular weight tau protein also suggests that it, like low molecular weight tau, is an elongated hydrophilic molecule. This cDNA should allow us to study the role of the domains specific to these tau forms in the specialization of the peripheral nervous system and for study of their expression in normal and pathological states.
Couchie
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Institut National de la Santé et de la Recherche Médicale U282-Centre National de la Recherche Scientifique Unité Associée, Hôpital Henri Mondor, Créteil, France.
Mavilia
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C
Georgieff
I S
IS
Liem
R K
RK
Shelanski
M L
ML
Nunez
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D015723:Gene Library; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D010525:Peripheral Nerves / Q000502:physiology*; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics*
D012333:RNA, Messenger; D016875:tau Proteins; D011061:Poly A; D012313:RNA; D004247:DNA