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bioRxiv · 10.1101/2019.12.12.873810

The lipid transfer function of RDGB at ER-PM contact sites is regulated by multiple interdomain interactions.

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

In Drosophila photoreceptors, following Phospholipase C-{beta} activation, the phosphatidylinositol transfer protein (PITP) RDGB, is required to maintain lipid homeostasis at endoplasmic reticulum (ER) plasma membrane (PM) membrane contact sites (MCS). Depletion or mis-localization of RDGB results in multiple defects in photoreceptors. Previously, interaction between the FFAT motif of RDGB with the integral ER protein dVAP-A was shown to be important for its localization at ER-PM MCS. Here, we report that in addition to FFAT motif, a large unstructured region (USR1) of RDGB is required to support the RDGB/dVAP-A interaction. However, interaction with dVAP-A alone is insufficient for accurate localization of RDGB: this also requires association of RDGB with apical PM, through its C-terminal LNS2 domain. Deletion of LNS2 domain results in complete mis-localisation of RDGB and also induces large mis-regulated interdomain movements abrogating RDGB function. Thus, multiple independent interactions between individual domains of RDGB supports its function at ER-PM MCS.

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Basak, B., Krishnan, H., Raghu, P.. 2019-12-12. The lipid transfer function of RDGB at ER-PM contact sites is regulated by multiple interdomain interactions.. https://doi.org/10.1101/2019.12.12.873810

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