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Four repeat MAP2 isoforms in human and rat brain
1California Institute of Technology, Division of Biology 216-76, Pasadena 91125.
Abstract:
In mammalian brain, variations in the primary structure of the characterized microtubule-associated protein 2 (MAP2) isoforms have only been observed in their projection domains whose length determines the spacing between neighboring microtubules. We now report that, as with MAP4 and tau, MAP2 isoforms containing four (4R) instead of three (3R) tandem repeats in their microtubule binding domains do exist in human and rat brain. The additional sequence, inserted between the first and second repeat of the 3R-MAP2 messages, appears on mRNAs encoding both high and low molecular weight (Hwt and Lwt) rat MAP2 variants. In contrast to the corresponding 3R-messages, 4R-Hwt MAP2 concentrations decrease during early postnatal rat brain development, while the amount of 4R-Lwt MAP2 messages remains constant. In general, 4R-/3R-MAP2 mRNA ratios appear to be low with the highest levels of 4R-messages found in the cerebellum.
Insights
New microtubule-associated protein 2 (MAP2) isoforms with four (4R) repeats, not three (3R), exist in mammalian brain. These 4R-MAP2 variants show developmental changes in rat brain, with higher levels in the cerebellum.
Area of Science:
- Neuroscience
- Molecular Biology
- Protein Isoforms
Background:
- Microtubule-associated protein 2 (MAP2) is crucial for microtubule stability in mammalian brain.
- Known MAP2 isoforms differ in projection domains, affecting microtubule spacing.
- Variations in microtubule-binding domains of MAPs like MAP4 and tau are documented.
Purpose of the Study:
- To identify and characterize novel MAP2 isoforms in human and rat brain.
- To investigate the presence and distribution of MAP2 isoforms with varying tandem repeats in the microtubule-binding domain.
- To examine the developmental expression patterns of these novel MAP2 isoforms in the rat brain.
Main Methods:
- Analysis of mRNA sequences to identify variations in MAP2 tandem repeats.
- Quantitative assessment of different MAP2 mRNA variants (3R vs. 4R) in brain tissue.
- Comparison of 4R-MAP2 mRNA levels during early postnatal rat brain development.
Main Results:
- Discovery of MAP2 isoforms containing four (4R) tandem repeats in the microtubule-binding domain, in addition to the known three (3R) repeats, in human and rat brain.
- The additional sequence in 4R-MAP2 is located between the first and second repeat of the 3R-MAP2 sequence.
- Expression analysis revealed that 4R-Hwt MAP2 mRNA levels decrease during early postnatal development in rats, while 4R-Lwt MAP2 mRNA levels remain constant.
- 4R-MAP2 mRNA levels are generally low compared to 3R-MAP2, with the highest relative abundance observed in the cerebellum.
Conclusions:
- Mammalian brain harbors MAP2 isoforms with four tandem repeats in their microtubule-binding domains, expanding the known structural diversity of MAP2.
- The developmental regulation of 4R-Hwt MAP2 suggests a role in specific postnatal brain maturation processes.
- The regional distribution, particularly the enrichment in the cerebellum, points to specialized functions of 4R-MAP2 isoforms in distinct brain areas.