Meta-Biol

• Pathways

Phosphatidylinositol 4,5-bisphosphate (PIP2) at the plasma membrane (PM) constitutively controls many cellular functions, and its hydrolysis via receptor stimulation can mediate cell signalling. A steady delivery of phosphatidylinositol (PI) from its site of synthesis in the endoplasmic reticulum (ER) to the PM is essential to maintain PIP2 levels. In addition, phosphatidic acid (PA), generated from diacylglycerol in the PM, has to reach the ER for PI resynthesis. The ubiquitously-expressed membrane-associated phosphatidylinositol transfer proteins 1, 2 and 3 (PITPNM1,2,3) (Lev et al. 1999) detect PIP2 hydrolysis and translocate to ER-PM junctions where they mediate the exchange of PI for PA (Kim et al. 2015, Chang & Liou 2015). Defects in PITPNM3 can cause cone-rod dystrophy 5 (CORD5; MIM:600977), a retinal dystrophy manifested as progressive loss of central vision, defective color vision, and photophobia. The missense mutation Q626H lacks the N-terminal PIT domain needed for transport of phospholipids and renewal of photoreceptors membranes is impaired (Kohn et al. 2007).