Inhibition of des transcription by cerulenin is mediated by the length of phospholipids acyl chains

PORRINI, L ; MANSILLA, MC; DE MENDOZA, D

Potrero de los Funes, San Luis

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2011

SAIB

The Des pathway of B. subtilis regulates the expression of the acyl-lipid desaturase, Des, thereby controlling the synthesis of unsaturated fatty acids from saturated phospholipid precursors. This pathway is regulated by a two-component system composed of a membrane-associated kinase, DesK, and a soluble transcriptional regulator, DesR, which stringently controls transcription of the des gene. This pathway is activated in response to a decrease in membrane fluidity provoked by a temperature downshift. However, very little is known about how DesK discriminates the surrounding lipid environment to promote membrane remodeling upon a drop in membrane fluidity. Here we report that inhibition of fatty acid FA) biosynthesis by cerulenin represses the expression of des gene. The FA profiles strongly suggest that cerulenin affects the signaling state of  DesK by increasing the incorporation of the lower-melting-point shorter-chain fatty acids into membrane phospholipids. We confirmed this hypothesis analyzing des expression in a mutant that conditionally expresses plsC (which encodes an acyltransferase). We show that strains with plsC depletion possess membranes with very long chain FA which lead to des overexpression at higher temperatures. These results provide the first in vivo evidence that pinpointed the membrane thickness as a signal used by cold sensors to maintain thermal homeostasis.