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. Author manuscript; available in PMC: 2021 Mar 27.
Published in final edited form as: Trends Neurosci. 2020 May 17;43(7):493–504. doi: 10.1016/j.tins.2020.04.007

Figure 1. Structure of (A) Low-Molecular-Weight (LMW) Tau and (B) Big Tau.

Figure 1.

(A) (i) The transcriptional organization of LMW human tau with exons 2/3 (N1 and N2 at the N-terminal) and exon 10 (R2 at the microtubule binding domain) as alternative splicing exons, which are developmentally regulated. LMW tau lacks exons 6 and 8. These transcriptional events give rise to 6 LMW isoforms. (ii) The largest 4R isoforms, with both N1/N2 comprising 441 amino acids, show on Western blots with apparent MW of 48–67 kDa (the true MW being 37–46 kDa). The tau protein comprises the microtubule (MT)-assembly domain, which includes the C-terminal region and the four microtubule-binding repeats (R1–4) and the N-terminal projection domain, including the N-terminal N1 and N2 exons and part of the proline-rich region. (B) Big tau (structure shown for rat) is an isoform that includes exons 4a and alternatively spliced exon 6, expressing proteins of apparent MW of 110 kDa. Big tau has a similar microtubule-assembly domain to LMW tau, but has an N-terminal projection domain that is 510 aa, which is more than double the size relative to the projection domain of LMW tau. Abbreviations: CTR, C-terminal region; MTBR, MT-binding region; NTR, N-terminal region; PRR, proline-rich region.