Abstract
Presentation Description :
PERP is a plasma membrane (PM)-localised apoptosis effector protein that was identified as a key determinant of tumour aggressiveness and metastasis risk, being significantly downregulated in monosomy 3 uveal melanoma (UM). Its unexpected interaction with the major endoplasmic reticulum (ER) calcium pump SERCA2b was recently identified and validated in UM cells. Significantly, this interaction was shown to occur at points of contact between the ER and PM and increased during both ER stress and SERCA2b-mediated apoptosis. The PERP-SERCA2b complex appears to directly communicate apoptosis signals from the cell surface to the ER, likely via calcium transfer. The findings underpin the firstly described apoptosis mechanism governing apoptosis involving ER-PM points of contact and indicate that PERP-deficient UM tumours lack a functional ER-PM junctional axis for apoptosis induction involving calcium signals.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.