FIGURE 3.

Endoplasmic reticulum-endosome MCSs in normal and cancer cells overexpressing STARD3. The sterol-transfer protein STARD3 promotes the formation of MCSs between late endosomes (LE) and the endoplasmic reticulum (ER), where it mediates cholesterol transport. Tethering of ER and LE occurs through the interaction of the LE-membrane anchored STARD3 (via its FFAT-like motif) with the integral ER proteins VAPs. In cancer cells, overexpression of STARD3 possibly induces the formation of aberrant LE-ER MCSs thereby inhibiting further endosomal maturation. Endosomal maturation is commonly associated with Rab5 to Rab7 switch and with PI3P to PI(3,5)P₂. MSP, major sperm protein domain.