Dividing Cells Regulate Their Lipid Composition and Localization

Abstract

SummaryAlthough massive membrane rearrangements occur during cell division, little is known about specific roles that lipids might play in this process. We report that the lipidome changes with the cell cycle. LC-MS-based lipid profiling shows that 11 lipids with specific chemical structures accumulate in dividing cells. Using AFM, we demonstrate differences in the mechanical properties of live dividing cells and their isolated lipids relative to nondividing cells. In parallel, systematic RNAi knockdown of lipid biosynthetic enzymes identified enzymes required for division, which highly correlated with lipids accumulated in dividing cells. We show that cells specifically regulate the localization of lipids to midbodies, membrane-based structures where cleavage occurs. We conclude that cells actively regulate and modulate their lipid composition and localization during division, with both signaling and structural roles likely. This work has broader implications for the active and sustained participation of lipids in basic biology.

Cytokinesis in Animal Cells

“…A special lipid composition at the furrowing plasma membrane contributes to successful cytokinesis (Brill et al 2011;Neto et al 2011;Atilla-Gokcumen et al 2014). For example, special lipids containing very long chain fatty acids are essential for cell shape deformation during cleavage furrow ingression (Szafer-Glusman et al 2008).…”

Metabolic control of the cell cycle

“…16 In line with these findings, the regulation of the lipidome is tightly synchronized with the cell cycle. 17 Silencing of lipid biosynthetic enzymes (including sphyngomyelin phospodiesterase 4, galactosylceramidase, diacylglycerol O-acyltransferase 2) leads to cell division defects and cytoskeletal changes in interphase cells. 17 Moreover, inhibition of cholesterol biosynthesis results in cell cycle arrest in G 0 .…”

“…17 Silencing of lipid biosynthetic enzymes (including sphyngomyelin phospodiesterase 4, galactosylceramidase, diacylglycerol O-acyltransferase 2) leads to cell division defects and cytoskeletal changes in interphase cells. 17 Moreover, inhibition of cholesterol biosynthesis results in cell cycle arrest in G 0 . 18 In addition, the lipid bilayers of the nuclear envelope and the plasma membrane display different Figure 1.…”

Enzyme Activities of the Ceramide Synthases CERS2–6 Are Regulated by Phosphorylation in the C-terminal Region

“…During cytokinesis, the levels of C22-and C24-ceramides are increased, and these VLC-ceramides are accumulated in the midbody (19). Knockdown of CERS2 or CERS4, which synthesize VLC-ceramides, results in cytokinesis failure (19). In the adipose tissue of obese humans, CERS6 mRNA expression and C16-ceramide are elevated, and increased CERS6 expression correlates with insulin resistance (6).…”

“…LC-ceramide, especially C16-ceramide, is generally pro-apoptotic, whereas VLC C24:0/C24:1-ceramides are antiapoptotic (17,18). During cytokinesis, the levels of C22-and C24-ceramides are increased, and these VLC-ceramides are accumulated in the midbody (19). Knockdown of CERS2 or CERS4, which synthesize VLC-ceramides, results in cytokinesis failure (19).…”