Intracellular trafficking terminal

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. 

The NRG1 C-terminal intracellular domain (NRG1-ICD) is required for membrane insertion, intracellular trafficking, and surface expression for Type I NRG1 isoforms. In addition, the NRG1-ICD mediates novel signal transduction events, at least for the Type III isoforms. The importance of the NRG1-ICD has been substantiated from several lines of direct and indirect evidence. 

Eukaryotic cells encode numerous proteins that terminate with a CAAX motif ( 100 in yeast, and several hundred in mammalian cells), and many have been directly demonstrated to be prenylated [1,2,4,6]. Their CAAX modifications can contribute significant hydrophobicity and profoundly influence the biological properties of these proteins. For example, CAAX modifications have been shown to affect membrane association, protein-protein interactions, intracellular trafficking, and/or the stability of the proteins to which they are appended [3]. 

Immunoc3d ochemical and ELISA studies showed that all N- and C-terminal receptor fragments capable of forming functional receptor complexes in the cotransfection experiments (see above) were stably inserted into lipid bilayers, even when expressed alone. Similar to the wild type m3 mAChR, the various receptor polypeptides were found both intraceUularly (ER/Golgi complex) as well as in the plasma membrane [20]. These observations suggest that the presence of the full-length receptor protein is not essential for membrane insertion and proper intracellular trafficking. 

---