Extrasomatic Targeting of MAP2, Vasopressin and Oxytocin mRNAs in Mammalian Neurons

Abstract

In eukaryotic cells, individual cellular subregions are functionally specialized. This is reflected by an uneven distribution of particular organelles and molecular components. Neurons possess an intrinsic polarity by which intercellular input and output sites are separated to dendrites and axons, respectively. To maintain this structural and functional polarity it is crucial for a neuron to target individual proteins to their correct subcellular destination. Extrasomatic mRNA trafficking and translation is thought to contribute to subcellular protein sorting in neurons. Different isoforms of the microtubuleassociated protein 2 (MAP2) and the respective mRNAs are both found in somata and dendrites of mammalian central nervous system neurons. MAP2 is known to influence microtubule stability and rigidity in vitro and in vivo. In neurons, MAP2 may be involved in regulating the morphology and function of dendritic spines and shafts. Extrasomatic transcript localization and local protein synthesis may provide a significant contribution to these regulatory processes. In magnocellular neurons of the hypothalamus, mRNAs encoding the vasopressin- and oxytocin-precursor protein are sorted to axons and dendrites. Both neuropeptides serve a dual function. After their secretion into the systemic circulation they act as hormones on different peripheral tissues. Moreover, they are released from dendrites into the central nervous system where they probably function as neurotransmitters/neuromodulators in events related to neuronal plasticity. In this chapter, we will focus on the recent identification of cis-acting extrasomatic targeting elements in MAP2, vasopressin and oxytocin mRNAs.