title: Regulation of maternal phospholipid composition and IP(3)-dependent embryonic membrane dynamics by a specific fatty acid metabolic event in C. elegans.
abstract: Natural fatty acids (FAs) exhibit vast structural diversity, but the functional importance of FA variations and the mechanism by which they contribute to a healthy lipid composition in animals remain largely unexplored. A large family of acyl-CoA synthetases (ACSs) regulates FA metabolism by esterifying FA to coenyzme A. However, little is known about how particular FA-ACS combinations affect lipid composition and specific cellular functions. We analyzed how the activity of ACS-1 on branched chain FA C17ISO impacts maternal lipid content, signal transduction, and development in Caenorhabditis elegans embryos. We show that expression of ACS-1 in the somatic gonad guides the incorporation of C17ISO into certain phospholipids and thus regulates the phospholipid composition in the zygote. Disrupting this ACS-1 function causes striking defects in complex membrane dynamics, including exocytosis and cytokinesis, leading to early embryonic lethality. These defects are suppressed by hyperactive IP(3) signaling, suggesting that C17ISO and ACS-1 functions are necessary for optimal IP(3) signaling essential for early embryogenesis. This study shows a novel role of branched chain FAs whose functions in humans and animals are unknown and uncovers a novel intercellular regulatory pathway linking a specific FA-ACS interaction to specific developmental events.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Kniazeva
authors.forename: Huali
authors.initials: H
authors.lastname: Shen
authors.forename: Tetyana
authors.initials: T
authors.lastname: Euler
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000201:enzymology / Q000648:ultrastructure; D005089:Exocytosis; D005227:Fatty Acids / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006066:Gonads / Q000201:enzymology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D005227:Fatty Acids; D006025:Glycosaminoglycans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010169:Palmitic Acids; D010743:Phospholipids; D034741:RNA, Small Interfering; D015544:Inositol 1,4,5-Trisphosphate