RT Journal Article
SR Electronic
T1 Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.19.345074
DO 10.1101/2020.10.19.345074
A1 Bishal Basak
A1 Harini Krishnan
A1 Padinjat Raghu
YR 2020
UL http://biorxiv.org/content/early/2020/10/19/2020.10.19.345074.abstract
AB During phospholipase C-β (PLC-β) signalling in Drosophila photoreceptors, the phosphatidylinositol transfer protein (PITP) RDGB, is required for lipid transfer at endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (MCS). Depletion of RDGB or its mis-localization away from the ER-PM MCS results in multiple defects in photoreceptor function. Previously, the interaction between the FFAT motif of RDGB and the integral ER protein dVAP-A was shown to be essential for accurate localization to ER-PM MCS. Here, we report that the FFAT/dVAP-A interaction alone is insufficient to localize RDGB accurately; this also requires the function of the C-terminal domains, DDHD and LNS2. Mutations in each of these domains results in mis-localization of RDGB leading to loss of function. While the LNS2 domain is necessary, it is not sufficient for the correct localization of RDGB, which also requires the C-terminal DDHD domain. The function of the DDHD domain is mediated through an intramolecular interaction with the LNS2 domain. Thus, interactions between the additional domains in a multi-domain PITP together lead to accurate localization at the MCS and signalling function.Competing Interest StatementThe authors have declared no competing interest.