STRUCTURE, REGIONAL AND DEVELOPMENTAL EXPRESSION OF RAT MAP2D, A MAP2 SPLICE VARIANT ENCODING 4 MICROTUBULE-BINDING DOMAINS

MAP2, a major component of microtubule polymers in neurons consists of high molecular weight (HMW) proteins MAP2a, MAP2b and a low molecular weight (LMW) MAP2c, expressed in the developing brain. These isoforms are produced from a single gene by alternative splicing and share identical C-termini encompassing 3 tandem repeats, critical in microtubule binding. We describe the structure: regional and developmental expression of a novel MAP2 splice variant, MAP2d, containing an insertion whose sequence is homologous to the three and four repeats of MAP2 and Tau respectively. This insertion is absent from the mRNAs encoding HMW MAP2. MAP2d mRNAs are expressed at higher levels than MAP2c in all adult nervous tissues of the rat, and are found at low levels in glial cell cultures when compared to primary cultures of cerebellar neurons. Splicing of the fourth repeat in mature Tau precedes that in MAP2d during rat brain development. The tardive expression of a four microtubule-binding domain LMW MAP2 suggests it could play in extended neurites a similar role as mature Tau in axons.