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Microtubule-associated protein-2 (MAP2) is the most abundant MAP in neurons, where its distribution is restricted to the somatodendritic compartment. This molecule undergoes developmentally regulated alternative splicing, resulting in at least two isoforms, a juvenile isoform (termed MAP2c) and a mature isoform (MAP2), with greatly different molecular masses. Spodoptera frugiperda (Sf9) cell expression of the juvenile versus the mature MAP2 isoform generates two distinct patterns of process outgrowth. The smaller juvenile isoform induces multiple short thin processes. Mature MAP2 tends to induce single processes that are considerably thicker than those processes induced by juvenile MAP2. We found important differences in the variability of spacing between microtubules and the number of microtubules along the processes induced by MAP2c and mature MAP2. MAP2c showed variability with most microtubules spaced as closely as with tau, but some spaced as far apart as with mature MAP2. Over their length, the mature MAP2 processes demonstrate proximo-distal taper, which corresponds to a narrowing of the spacing between microtubules from 90 nm to 40 nm. Moreover, there is a decreased number of microtubules in mature MAP2-induced processes whereas in tau and MAP2-induced processes, the number of microtubules is constant along the length. Based on these observations, we conclude that MAP2 isoforms can serve as architectural elements by establishing specific morphological features of processes and specific arrangements of their microtubules.

Juvenile and mature MAP2 isoforms induce distinct patterns of process outgrowth.