The SAC1 phosphatase domain of synaptojanin ‐1 is activated by interacting with polyunsaturated fatty acid‐containing phosphatidic acids

Although there are many phosphatidic acid (PA) molecular species based on its fatty acyl compositions, their interacting partners have been poorly investigated. Here, we identified synaptojanin-1 (SYNJ1), Parkinson ’s disease-related protein that is essential for regulating clathrin-mediated synaptic vesicle endocytosis via dually dephosphorylating D5 and D4 position phosphates from phosphatidylinositol (PI) (4,5)-bisphosphate, as a 1-stearoyl-2-docosahexaenoyl (18:0/22:6)-PA-binding protein. SYNJ1 failed to substantially associate with other acidic phospholipids. Although SYNJ1 interacted with 18:0/20:4-PA in addition to 18:0/22:6-PA, the association of the enzyme with 16:0/16:0-, 16:0/18:1-, 18:0/18:0-, or 18:1/18:1-PA was not considerable. 18:0/20:4- and 18:0/22:6-PAs bound to SYNJ1 via its SAC1 dom ain, which preferentially hydrolyses D4 position phosphate. Moreover, 18:0/20:4- and 18:0/22:6-PA selectively enhanced the D4-phosphatase activity, but not the D5-phosphatase activity, of SYNJ1.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research