Diversity of High‐Molecular‐Weight τ Proteins in Different Regions of the Nervous System

We show in this work that high‐molecular‐weight (HMW) τ transcripts are present in all the regions of the CNS and PNS studied, i.e., the dorsal root ganglia (DRG), spinal cord, cerebellum, and forebrain. However, the relative amount of HMW and low‐molecular‐weight (LMW) τ variants and their sequence vary depending on the region. Two HMW τ variants that contain either both exons 4A and 6 or only exon 6 have been identified in the adult spinal cord by PCR amplification and sequenced. In contrast, a single HMW τ variant that contains exon 4A but not exon 6 was detected in the adult rat DRG. This means that at least part of the HMW τ expressed in the spinal cord is produced locally and not transported within this structure by fibers arising in the DRG. The expression of the HMW τ isoforms is developmentally regulated both quantitatively and qualitatively in the spinal cord. At immature stages very low levels of the HMW τ transcript containing both exons 4A and 6 are expressed, whereas the τ species containing only exon 6 is absent. Rat forebrain, rat cerebellum, and human forebrain express much lower levels of HMW τ transcripts compared with the spinal cord and the DRG. Their sequence contains both exons 4A and 6, i.e., is identical to that of the major HMW τ transcript detected in the adult rat spinal cord. The minor spinal cord species that contains only exon 6 was not identified in the rat forebrain and rat cerebellum but was present among the human brain PCR fragments. These data demonstrate that the family of HMW τ proteins is heterogeneous and that it includes transcripts containing exon 4A, 6, or both. Six of 15 exons of the τ gene are alternatively spliced, and the pattern of splicing varies quantitatively and/or qualitatively depending on the region of the nervous system and on the developmental stage.