A subgroup of these genes was involved in lipid metabolism

In cells with decreased expression of NTAL due to NTAL KO or NTAL KD, gene expression is Gluconate Calcium changed when compared to WT cells. After activation of NTAL-deficient cells, LAT is phosphorylated by SYK. However, because of NTAL absence, LAT is more phosphorylated than in WT cells. This leads to increased i and transcriptional regulation which is different from WT cells. These processes contribute to enhanced response to Ag in NTAL-deficient cells, including enhanced degranulation, calcium response, chemotaxis and depolymerization of F-actin. Unexpected findings in this study were NTAL-dependent changes in the expression of a number of genes related to metabolism and biosynthetic processes. A subgroup of these genes was involved in lipid metabolism, including synthesis of cholesterol. Although decreased transcription of several genes involved in cholesterol synthesis was confirmed by RT-qPCR, no significant difference in total amount of cellular cholesterol was detected between WT and NTAL-deficient cells. Yet, surprisingly, we found that pretreatment of BMMCs with MbCD had different effect on NTAL KO and WT cells. In NTAL KO cells MbCD significantly inhibited chemotaxis at all concentrations of MbCD tested, whereas in WT cells MbCD either slightly, but reproducibly increased chemotaxis at a low concentration or had no significant effect at higher concentrations. MbCD is known to remove cholesterol from the cells and therefore one can hypothesize that enhanced chemotaxis in NTAL-deficient cells is regulated in part by plasma membrane cholesterol distribution. Molecular mechanism of the cholesterol-dependent regulations of chemotaxis is poorly understood, but could be related to TPPB differences in synthesis and/or distribution of cholesterol into plasma membrane sheets. One such possible mechanism has been recently described in macrophages with defect in ATP-binding cassette transporters ABCA1 and ABCG1, which are involved in the movement of cholesterol from the inner to the outer leaflet of the plasma membrane and play role in chemotaxis towards C5a chemoattractant.

Leave a Reply

Your email address will not be published.