Posttranslationale Regulation der Transportaktivität humaner kationischer Aminosäuretransporter (human cationic aminoacid transporter: hCATs)
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Abstract
Cells depend on transporters for communication, interaction, and the selective uptake of nutrients and other molecules. Despite their importance, the intricate regulatory mecha-nisms that govern transporter activity and surface expression are not fully understood for many of these vital membrane proteins. This work investigated the post-translational regulation of human cationic amino acid transporters (hCATs) by protein kinase C (PKC) involving Rho-GTPases (Cdc42, Rac1, and RhoA) and other potentially involved proteins.
The central finding of the work is that both PKC and Rho-GTPases, especially Cdc42, play a crucial role in modulating the transport activity of all four hCAT isoforms. Activation of PKC leads to a significant reduction in arginine uptake by the hCATs. This effect was demonstrated in Xenopus laevis oocytes as a model system and various human cell lines. Interestingly, the reduced arginine uptake is caused by the altered membrane localization of the transporters (induced endocytosis).
An important aspect of this work is the investigation of the interplay of Rho-GTPases in regulating hCAT transporters showing the involvement of these GTPases in adapting transporter activity to meet cellular arginine demand. The results suggest that the simul-taneous activation of PKC and Rho-GTPases could lead to complex regulation of hCAT transporters, involving a reduced localization of the transporters in the plasma mem-brane.
The importance of membrane localization for the function of hCAT transporters was par-ticularly emphasized in this work. Understanding the mechanisms that regulate mem-brane proteins, especially transporter proteins, is of central importance, as they represent both targets and sensors for the cell's environment.
In summary, this research makes an important contribution to understanding the com-plex regulation of amino acid transporters, especially hCATs. The results show that PKC and Rho-GTPases play a crucial role in modulating transport activity and that membrane localization of the transporters is an important factor for their function. The interaction between PKC and Rho-GTPases could represent a finely tuned system that controls amino acid uptake as needed.