HETEROGENEITY IN THE PHOSPHORYLATION OF MICROTUBULE-ASSOCIATED PROTEIN MAP1B DURING RAT-BRAIN DEVELOPMENT

The patterns of isoforms and of immunoreactivity of the microtubule-as sociated protein MAP1B toward a panel of antibodies to phosphorylation -sensitive epitopes are different in distinct rat brain regions and ch ange during development. This suggests the occurrence of a considerabl e degree of heterogeneity in the phosphorylation state of rat brain MA P1B. It appears that MAP1B can be phosphorylated at multiple sites tha t may be conventionally classified into at least two modes of phosphor ylation. Mode I of phosphorylation induces significant upward shifts i n the electrophoretic mobility of the protein, giving rise to ''high'' MAP1B isoforms, whereas the mode II of MAP1B phosphorylation does not greatly affect the electrophoretic mobility of the protein. These MAP 1B phosphorylation modes are differentially regulated throughout devel opment and show some regional specificity. Cytosolic MAP1B is highly p hosphorylated both at mode I and mode II sites in the developing rat b rain, as well as in the adult olfactory bulb, where axonal growth take s place. In most adult rat brain regions, cytosolic MAP1B is highly ph osphorylated at mode II sites but largely dephosphorylated at certain mode I sites. However, MAP1B present in the particulate fraction of mo st rat brain region homogenates may be partially dephosphorylated at c ertain mode II sites, although it contains some phosphorylated mode I sites. These data are compatible with the view that different protein kinases, possibly including casein kinase II and proline-directed prot ein kinases, might regulate the state of phosphorylation of MAP1B in d istinct localizations along the development of different neuronal popu lations in the brain.