The Role of Selective Transport in Neuronal Protein Sorting

Abstract

To assess whether selective microtubule-based vesicle transport underlies the polarized distribution of neuronal proteins, we expressed green fluorescent protein- (GFP-) tagged chimeras of representative axonal and dendritic membrane proteins in cultured hippocampal neurons and visualized the transport of carrier vesicles containing these proteins in living cells. Vesicles containing a dendritic protein, transferrin receptor (TfR), were preferentially transported into dendrites and excluded from axons. In contrast, vesicles containing the axonal protein NgCAM (neuron-glia cell adhesion molecule) were transported into both dendrites and axons. These data demonstrate that neurons utilize two distinct mechanisms for the targeting of polarized membrane proteins, one (for dendritic proteins) based on selective transport, the other (for axonal proteins) based on a selectivity "filter" that occurs downstream of transport.

The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro

“…Since the 5-HT 2A receptor is abundant in cortical pyramidal neurons, it is likely that targeting signals identified from studies that are conducted in cultured cortical pyramidal neurons bear more physiological relevance than those from polarized epithelial cells. Indeed, the "epithelial metaphor" (Colman, 1999), which posits that neuronal and polarized epithelial cells share similar subcellular sorting apparatuses (Dotti and Simons, 1990), has proven to be limited in that apical and basolateral surfaces of the plasma membrane in epithelial cells do not always correspond to the axonal and dendritic compartments of neurons (West et al, 1997;Jareb and Banker, 1998;Wozniak and Limbird, 1998;Ghavami et al, 1999;Stowell and Craig, 1999;Burack et al, 2000). The cortical culture, however, has its own intrinsic limitations in that we cannot differentiate apical from basilar dendrites in pyramidal neurons, and we accordingly frame our study within the boundary of axonal versus dendritic targeting.…”

“…It appears that axonal and dendritic targeting involve different components of the sorting apparatus (Foletti et al, 1999). For example, different populations of carrier vesicles are responsible for delivering dendritic and axonal proteins (Burack et al, 2000). Selective sorting to dendrites relies on microtubule-based transport, whereas preferential distribution to axons involves selective retention at the destination (Burack et al, 2000).…”

“…For example, different populations of carrier vesicles are responsible for delivering dendritic and axonal proteins (Burack et al, 2000). Selective sorting to dendrites relies on microtubule-based transport, whereas preferential distribution to axons involves selective retention at the destination (Burack et al, 2000). Furthermore, intact lipid rafts, consisting of detergent-insoluble glycosphingolipid-cholesterol complexes, appear essential for the targeting of some axonal proteins (Ledesma et al, 1998), but no such requirement has been reported for dendritic proteins.…”

RAB-10 Is Required for Endocytic Recycling in theCaenorhabditis elegansIntestine

“…Equivalent GFP-fusions for these three proteins have previously been shown to be functional and traffic normally in mammalian cells and/or C. elegans. First we expressed the human transferrin receptor (hTfR-GFP), a marker for clathrin-dependent uptake and rme-1-dependent recycling in mammalian cells (Yamashiro et al, 1984;Burack et al, 2000;Lin et al, 2001). Next we expressed the ␣-chain of the human IL-2 receptor TAC (hTAC-GFP), a marker for clathrin-independent endocytosis and rme-1-dependent recycling in mammalian cells (Caplan et al, 2002;Naslavsky et al, 2004).…”

Molecular Cloning and Characterization of Phocein, a Protein Found from the Golgi Complex to Dendritic Spines

“…Information gathered and processed by the dendrites flow through the axons to the synapses. The structure and composition of axons and dendrites are quite different, particularly concerning their respective plasma membranes, cytoskeleton (Gunning et al, 1998;Baas, 1999), and proteins involved in vesicular traffic, such as motor proteins (Foletti et al, 1999;Burack et al, 2000). Striatin is a neuronal, intracellular protein strictly expressed in the somato-dendritic compartment, including spines, of subsets of neurons: thus, it can be considered as a marker of neuronal polarity (Castets et al, 1996;Kachidian et al, 1998;Salin et al, 1998).…”