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bioRxiv · 10.1101/2020.10.19.345074

Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites

Basak, B.·Krishnan, H.·Raghu, P.
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Abstract

During phospholipase C-{beta} (PLC-{beta}) 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.

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Basak, B., Krishnan, H., Raghu, P.. 2020-10-19. Interdomain interactions regulate the localization of a lipid transfer protein at ER-PM contact sites. https://doi.org/10.1101/2020.10.19.345074

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