Drosophila lysophospholipid acyltransferases are specifically required for germ cell development - PubMed (original) (raw)

(A) Phylogram of the MBOAT enzymes from S. cerevisiae (Sc), Drosophila melanogaster (Dm), and Homo sapiens (Hs) made using the ClustalW algorithm. Farjavit is the Drosophila homologue of human MBOAT7, a lyso-PI acyltransferase (LPIAT). Nessy is the Drosophila homologue of human MBOAT5, also known as lyso-PC acyltransferase 3 (LPCAT3), and Oysgedart is the Drosophila homologue of human MBOATs 1 and 2. Other MBOAT family members include the Hedgehog acyltransferases (Rasp, HHAT, and HHATL), the Wnt acyltransferases (Porcupine and PORCN), the Ghrelin acyltransferase (GOAT/MBOAT4), the GPI remodeling acyltransferase Gup1p, the diacylglycerol acyltransferases (DGAT1 and Midway), and the cholesterol acyltransferases (ACATs 1 and 2, Are1p and Are2p, and Drosophila CG8112). Transmembrane containing protein 4 (TMC4) appears to be an “orphan” human MBOAT. Color blocks indicate substrate preferences as follows: red, lysophospholipid; yellow, Hedgehog; light green, diacylglycerol; dark green, cholesterol; blue, Wnt. Sequences were collected from NCBI Homologene (

http://www.ncbi.nlm.nih.gov/sites/entrez/query.fcgi?db=homologene

). (B) Schematic of phospholipid (PL) remodeling via the Lands pathway. Remodeling is initiated by a PLA2, which releases a free fatty acid (FFA) and a lysophospholipid. Acyl-CoA is generated from FFA via a CoA-ligase (FACL), and used by a lysophospholipid acyltransferase (LPLAT) to regenerate the PL. R is the chemical group specific for each phospholipid class: hydroxyl (PA), choline (PC), ethanolamine (PE), glycerol (PG), serine (PS), or inositol (PI). (C) Partial alignment of MBOAT family LPLATs from S. cerevisiae, D. melanogaster, and H. sapiens showing the conserved active site histidine (red asterisk).