Intracellular trafficking

Since the SUMO pathway affects multiple pathways ranging from transcription, DNA repair, and intracellular trafficking over cell signaling and cell cycle control to basic metabolism, it is not suiprising that links to diseases and viral assaults are emerging. However, the field is not yet at a stage sufficiently developed for pharmacological intervention. Below we will describe selected examples for links of the SUMO pathway to diseases and viral functions. 

It is the a2A/D-adrenoceptor that predominates in the locus coeruleus and this subtype seems to be responsible for reducing neuronal excitability and transmitter release. Strangely, immunocytochemical studies suggest that most a2c-receptors are intracellular. The explanation for this finding and its functional implications are as yet unknown but it could reflect differences in intracellular trafficking of different receptor subtypes. 

Recent evidence indicates that the 5-HT transporter is subject to post-translational regulatory changes in much the same way as neurotransmitter receptors (Blakeley et al. 1998). Protein kinase A and protein kinase C (PKC), at least, are known to be involved in this process. Phosphorylation of the transporter by PKC reduces the Fmax for 5-HT uptake and leads to sequestration of the transporter into the cell, suggesting that this enzyme has a key role in its intracellular trafficking. Since this phosphorylation is reduced when substrates that are themselves transported across the membrane bind to the transporter (e.g. 5-HT and fi -amphetamine), it seems that the transport of 5-HT is itself linked with the phosphorylation process. Possibly, this process serves as a homeostatic mechanism which ensures that the supply of functional transporters matches the demand for transmitter uptake. By contrast, ligands that are not transported (e.g. cocaine and the selective serotonin reuptake inhibitors (SSRIs)) prevent the inhibition of phosphorylation by transported ligands. Thus, such inhibitors would reduce 5-HT uptake both by their direct inhibition of the transporter and by disinhibition of its phosphorylation (Ramamoorthy and Blakely 1999). 

Hanada, K., Kumagai, K., Tomishige, N., and Kawano, M. 2007. CERT and intracellular trafficking of cer-amide. Biochim. Biophys. Acta, 1771 (6) 644—653. 

Lacerda, L. et al. (2007) Intracellular trafficking of carbon nanotubes by confocal laser scanning microscopy. Advanced Materials, 19 (11),... 

Arden JR, Segredo V, Wang Z et al. Phosphorylation and agonist-specific intracellular trafficking of an epitope-tagged K-opioid receptor expressed in HEK 293 cells. J Neurochem 1995 65 1636-1645. 

Morris, R.E., and Saelinger, C.B. (1984) Visualization of intracellular trafficking use of biotinylated ligands in conjunction with avidin-gold colloids./. Histochem. Cytochem. 32, 124-128. 

Several intracellular trafficking pathways converge at lysosomes 150 Both constitutive and regulated neuroendocrine secretion pathways exist in cells of the nervous system 151... 

Neurons constitute the most striking example of membrane polarization. A single neuron typically maintains thousands of discrete, functional microdomains, each with a distinctive protein complement, location and lifetime. Synaptic terminals are highly specialized for the vesicle cycling that underlies neurotransmitter release and neurotrophin uptake. The intracellular trafficking of a specialized type of transport vesicles in the presynaptic terminal, known as synaptic vesicles, underlies the ability of neurons to receive, process and transmit information. The axonal plasma membrane is specialized for transmission of the action potential, whereas the plasma... 

Calver, A. R., Robbins, M. J., Cosio, C., et al. (2001) The C-terminal domains of the GABAb receptor subunits mediate intracellular trafficking but are not required for receptor signaling. J. Neurosci. 21,1203-1210. 

Bednarek SV, Raikhel NV. Intracellular trafficking of secretory proteins. Plant... 

The fundamental process of transferring a solute from the environment, across a cell(s) to the blood involves the common steps of adsorption, influx, intracellular trafficking or distribution, and efflux to the blood. This process applies to physiologically important solutes like Na+ and amino acids, and applies equally to solutes of environmental concern, such as toxic metals. Animals spend a significant portion of their energy budgets on osmotic regulation indeed, at the... 

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