Expression of high molecular weight tau in the central and peripheral nervous systems

• Published in: Journal of cell science Vol. 105; no. 3; pp. 729 - 737
• Main Authors: GEORGIEFF, I. S, LIEM, R. K. H, COUCHIE, D, MAVILIA, C, NUNEZ, J, SHELANSKI, M. L
• Format: Journal Article
• Language: English
• Published: Cambridge Company of Biologists 01.07.1993
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Central Nervous System - growth & development; Central Nervous System - metabolism; Cloning, Molecular; DNA, Complementary - genetics; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - metabolism; Gene Expression; General aspects. Models. Methods; Immunohistochemistry; In Situ Hybridization; Molecular Sequence Data; Molecular Weight; Peripheral Nervous System - growth & development; Peripheral Nervous System - metabolism; Polymerase Chain Reaction; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; tau Proteins - chemistry; tau Proteins - genetics; Vertebrates: nervous system and sense organs; Proteins; Peripheral nervous system; Spinal cord; Central nervous system; Axon; Cytoskeleton; Spinal ganglion; Microtubule; Gene expression; Spinal root
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.105.3.729

Using a novel PCR approach, we have cloned a cDNA encoding the entire high molecular weight tau molecule from rat dorsal root ganglia. The resulting 2080 bp cDNA differs from low molecular weight rat brain tau by the insertion of a novel 762 bp region (exon 4a) between exons 4 and 5. This cDNA clone is identical in sequence with a high molecular weight tau (HMW) cDNA from rat PC12 tumor cells and is closely related to a HMW tau cDNA from mouse N115 tumor cells. In vitro transcription/translation produces a protein that migrates on SDS-PAGE with the same apparent molecular weight as HMW tau purified from rat sciatic nerve. The HMW tau protein is generated from an 8 kb mRNA, which can be detected by northern blots in peripheral ganglia, but not in brain. A more sensitive assay using PCR and Southern blot analysis demonstrates the presence of exon 4a in spinal cord and in retina. In combination with immunohistochemical studies of spinal cord, these data suggest that HMW tau, though primarily in the peripheral nervous system, is also expressed in limited areas of the central nervous system, although its presence cannot be detected in the cerebral cortices.