STRUCTURAL COMPARTMENTS WITHIN NEURONS - DEVELOPMENTALLY-REGULATED ORGANIZATION OF MICROFILAMENT ISOFORM MESSENGER-RNA AND PROTEIN

The microfilament system is thought to be a crucial cytoskeletal compo nent regulating development and mature function of neurons. The intrac ellular distribution of the microfilament isoform components, actin an d tropomyosin (Tm), in neurons primarily in vivo, has been investigate d at both the mRNA and the protein level using isoform specific ribopr obes and antibodies. Our in vivo and in vitro studies have identified at least six neuronal compartments based on microfilament isoform mRNA localization: the developing soma, the mature soma, growth cone, deve loping axon hillock/proximal axon, Mature somatodendritic and mature a xonal pole soma. Protein localization patterns revealed that the isofo rms were frequently distributed over a wider area than their respectiv e mRNAs, suggesting that isoform specific patterns of mRNA targeting m ay influence, but do not absolutely determine, microfilament isoform l ocation. Tm4 and Tm5 showed identical mRNA targeting in the developing neuron but distinct protein localization patterns. We suggest that in this instance mRNA location may best be viewed as a regulated site of synthesis and assembly, rather than a regulator of protein localizati on per se. In addition, Tm5 and p-actin mRNA and protein locations wer e developmentally regulated, suggesting the possibility that environme ntal signals modulate targeting of specific mRNAs and their proteins. Thus, developmentally regulated mRNA localization and positional trans lation may act in concert with protein transport to regulate neuronal microfilament composition and consequently neuronal structure.