TRANSGENIC EXPRESSION OF EMBRYONIC MAP2 IN ADULT-MOUSE BRAIN - IMPLICATIONS FOR NEURONAL POLARIZATION

The major neuronal microtubule-associated protein MAP2 is selectively localized in dendrites, where its expression is under strong developme ntal regulation. To learn more about its potential effects on neuronal morphogenesis and its sorting within the neuronal cytoplasm, we have raised transgenic mice that express high levels of the embryonic form, MAP2c, in the adult brain. One transgenic line expressed higher level s of MAP2c than endogenous adult MAP2. This had no detectable effect o n either the arrangement or morphology of neurons, suggesting that alt hough MAP2c is necessary for neuronal morphogenesis it is not involved in its regulation. Like endogenous adult MAP2, transgenic MAP2c was p resent in dendrites but not axons, indicating that the signal responsi ble for its cytoplasmic sorting is contained within the 1.5 kb of its coding sequence. In situ hybridization with specific probes showed tha t transgenic MAP2c mRNA was limited to cell bodies. Thus, the dendriti c localization of MAP2c protein cannot be the result of previous trans port of its mRNA but must depend on a signal associated with the prote in itself. Furthermore, because the amino acid sequence of MAP2c is pr esent in all forms of MAP2, this signal is also contained within adult high-M(r) MAP2 protein. This raises the possibility that, rather than the conventional scheme of mRNA sorting preceding protein localizatio n, the transport of adult MAP2 mRNA into dendrites could depend on it being part of a translation complex in which the targeting signal is o n the nascent protein.