A putative mechanism of SLC5A3-mediated myo-inositol release during RVD.

<p><b>A:</b> Under isotonic conditions the SLC5A3 protein is mainly localized in the cytosolic vesicles and its mRNA level is low. The plasma membrane permeability to SOOs and electrolytes is poor. <b>B:</b> Exposure of cells to a strongly hypotonic solution, e.g. 100-mOsm sucrose, causes rapid volume increase followed by cell shrinkage via RVD (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119990#pone.0119990.g001" target="_blank">Fig. 1</a>). The swelling-associated increase in the plasma membrane area is achieved (i) by unfolding of microvilli and (ii) by exocytotic fusion of cytosolic vesicles [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119990#pone.0119990.ref023" target="_blank">23</a>]. The fusion of vesicles carrying SLC5A3 protein leads to the incorporation of this transporter into the plasma membrane. The SLC5A3-mediated efflux of myo-inositol and related SOO contributes to cell shrinkage (RVD) and restoration of the original isotonic cell volume. <b>C:</b> During RVD, the cells recover the original membrane impermeability to myo-inositol (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119990#pone.0119990.g001" target="_blank">Fig. 1</a>), presumably, via the endocytosis of excessive plasma membrane along with reinternalization and, possibly, lysosomal degradation of SLC5A3. The increased mRNA and protein expression of SLC5A3 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119990#pone.0119990.g006" target="_blank">Fig. 6</a>) suggest that <i>de novo</i> synthesis of SLC5A3 occurs to restore the depleted cytoplasmic pool of the transporter.