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Genes Dev ; 26(6): 554-66, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22426533

RESUMO

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.


Assuntos
Caenorhabditis elegans/embriologia , Ácidos Graxos/metabolismo , Inositol 1,4,5-Trifosfato/metabolismo , Ácidos Palmíticos/metabolismo , Fosfolipídeos/metabolismo , Animais , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/genética , Membrana Celular/enzimologia , Embrião não Mamífero/enzimologia , Embrião não Mamífero/ultraestrutura , Exocitose , Glicosaminoglicanos/metabolismo , Gônadas/enzimologia , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Fosfolipídeos/química , RNA Interferente Pequeno/genética
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