Subcellular RNA compartmentalization
Introduction
The highly polarized nature of neuronal cells of the central and peripheral nervous system requires elaborate and accurate sorting mechanisms of their macromolecular constituents. Intracellular transport is detrimental for the generation and maintenance of the polarized morphology and ultimately for cell communication within the neuronal network. Continuous redistribution of macromolecules is probably required upon formation of new synapses as well as remodelling of pre-existing ones, for instance during the course of learning and memory consolidation. How a neuron achieves the equipment of distinct microdomains with a defined assortment of proteins that are needed at particular sites for a cell to function as it does such as membrane-associated receptors and other factors involved in synaptic plasticity is still being investigated. Initially, it has been assumed that proteins are generally synthesized in the cell body and are subsequently delivered to sites that may be located at considerable distances from the cell somata, for instance in axons and dendrites. In recent years, however, a variety of mRNA species have been detected in neuronal processes indicating that a decentralized translation machinery might also be operative, at least in dendrites and in the initial axonal segment both of which possess protein synthesizing capacity (Steward and Levy, 1982; Steward and Ribak, 1986). Some RNAs are delivered to distal axonal segments [for review see Mohr and Richter (1995)] which are believed to lack components necessary for translation, at least in mammals (Lasek and Brady, 1981). Consequently, the physiological meaning of these transcripts has remained obscure. mRNA transport to distinct locations within the cell is not restricted to nerve cells but has been observed in various non-neuronal systems. Developing systems such as Xenopus and Drosophila oocytes and early embryos are particularly interesting models because mRNA transport is strictly controlled in a spatial and temporal manner and it is absolutely required to allow for correct body pattern formation [for review see St. Johnston (1995); Bassell and Singer (1997); Gavis (1997)]. While the molecular determinants of mRNA targeting in nerve cells are still largely unknown, studies performed in non-neuronal systems indicate the involvement of cis-acting signals inherent to the mRNA molecules to be transported and trans-acting protein factors which bind to these signals either directly or indirectly via protein/protein interactions to guide the RNAs to their ultimate intracellular destinations [for review see St. Johnston (1995); Bassell and Singer (1997); Gavis (1997)]. There is circumstantial evidence for similar mechanisms to exist in neurons. The present review will summarize our current knowledge of individual components of the subcellular mRNA transport machinery in nerve cells and the question concerning the functional significance of this process will be addressed.
Section snippets
Different classes of mRNAs are targeted to dendrites
Apart from BC1 RNA, a non-coding RNA polymerase III transcript (Tiedge et al., 1991) all of the few RNA species residing in dendrites of various nerve cells are mRNAs (Table 1). BC1 RNA forms part of a ribonucleoprotein particle and its function has not yet been determined (Kobayashi et al., 1992). This RNA is detectable in dendrites of various nerve cell types both in the rat central nervous system as well as in primary cultured neurons (Tiedge et al., 1991). Transcripts encoding the
mRNAs located in axons
While a clear physiological relevance, namely local protein biosynthesis, can be ascribed to mRNAs located in the dendrites of nerve cells, the role of transcripts residing in the axonal compartment is less clear. Notwithstanding, as summarized in Table 2, a variety of RNAs, often in substantial amounts, are clearly detectable in axons of various nerve cell types from vertebrates including mammals and invertebrates. Invertebrate neurons, however, differ considerably from those of vertebrates,
Conclusion and perspectives
The last few years have shown that specific mRNA sorting is observed in various eukaryotic cell types throughout the animal kingdom. It appears to be one of the fundamental mechanisms operative in cells in order to create and maintain polarity. Studying these phenomena in nerve cells is particularly interesting because neurons certainly represent one of the most complex cell types. They communicate via thousands of synapses with other nerve cells and their protein repertoire is extremely
Acknowledgements
The author thanks Dr Dietmar Richter (University of Hamburg) for helpful discussion and critical reading of the manuscript, Drs Dietmar Kuhl and Stefan Kindler (University of Hamburg) for their contribution of Fig. 1, Fig. 2, and the Deutsche Forschungsgemeinschaft for financial support.
References (102)
- et al.
mRNA and cytoskeletal filaments
Curr. Opin. Cell Biol.
(1997) - et al.
Cis-acting signals and trans-acting proteins are involved in tau mRNA targeting into neurites of differentiating neuronal cells
Int. J. Dev. Neurosci.
(1995) - et al.
Differential mRNA transport and the regulation of protein synthesis: selective sensitivity of Purkinje cell dendritic mRNAs to translational inhibition
Mol. Cell. Neurosci.
(1996) - et al.
Presence of neuropeptide messenger RNA in neuronal processes
Neurosci. Lett.
(1990) - et al.
Distinct spatial localization of specific mRNAs in cultured sympathetic neurons
Neuron
(1990) - et al.
Implication of 5′ coding sequences in targeting maternal mRNA to the Drosophila oocyte
Mechan. Dev.
(1997) - et al.
The distribution of glutamate receptors in cultured rat hippocampal neurons: postsynaptic clustering of AMPA-selective subunits
Neuron
(1993) - et al.
Molecular characterization of the dendritic growth cone: regulated mRNA transport and local protein synthesis
Neuron
(1996) - et al.
BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity
Neuron
(1992) - et al.
Staufen protein associates with the 3′ UTR of bicoid mRNA to form particles that move in a microtubule-dependent manner
Cell
(1994)