## 3 Role of Lipids for Membrane Function and Intracellular Transport
### Effect on Endocytosis and/or Retrograde Transport due to Manipulations of the Lipidome
#### 3.7.2 Studies Related to Ether Lipids  
Although PLs with ether-linked alkyl or alkenyl chains (PLs containing an alkenyl group are often called plasmalogens) make up 5-20% of lipids in many cells, there are so far surprisingly few studies of their importance for intracellular transport. The ether-linked chains are most commonly found in the _sn-1_ position, whereas the sn-2 position very often contains polyunsaturated fatty acyl (PUFA) chains such as arachidonic acid (C20:4). Ether-linked chains are found in several PL classes, but most often in the PE and PC classes. In most studies, PE ethers have been reported to be the dominant ether lipids, with alkenyl ethers dominating over alkyl ethers [167; 168; 169; 170; 171; 172]. For reviews of the biological function of ether lipids, see [168; 169; 173; 174; 175]. Addition of the ether lipid precursor hexadecylglycerol (HG) to HEp-2 cells resulted in a major increase in the ether lipids and a decrease in the GSLs, with approximately 25% reduction in total Gb3 (no changes in the Gb3 species distribution) [176]. This treatment provided very strong protection of the cells against Shiga toxin and even stronger protection against Stx2 [177]. \begin{table}
\begin{tabular}{c c c c c c c c c c c c} \hline \hline
**Treatment** & **Binding** & **Uptake 1** & **Endo \(\rightarrow\) Golgi** & **Golgi \(\rightarrow\) ER** & **Toxicity** & **Cer** & **CicKer** & **Gib3** & **AcrI PL** & **Ether PL** & **Other Information** \\ \hline \multirow{2}{*}{Fumninish 2} & \multirow{2}{*}{Skr \(\downarrow\downarrow\)} & \multirow{2}{*}{–} & \multirow{2}{*}{Skr \(\downarrow\downarrow\)} & \multirow{2}{*}{Skr \(\downarrow\downarrow\)} & \multirow{2}{*}{\(\downarrow\downarrow\)} & \multirow{2}{*}{\(\downarrow\downarrow\)} & \multirow{2}{*}{\(\downarrow\downarrow\)} & \multirow{2}{*}{\(\downarrow\downarrow\)} & \multirow{2}{*}{\(\downarrow\downarrow\)} & \multirow{2}{*}{PE \(\uparrow\uparrow\)} & \multirow{2}{*}{No effect on ricin} \\  & & & & & & & & & & & & & \\ \hline PDMP 3 & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & No effect on ricin \\ \hline HG 4 & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) & \(\times\) \\ \hline \multirow{2}{*}{Cell density 5} & \multirow{2}{*}{Skr \(\downarrow\downarrow\)} & \multirow{2}{*}{–} & \multirow{2}{*}{–} & \multirow{2}{*}{Skr \(\downarrow\downarrow\)} & \multirow{2}{*}{\(\uparrow\)} & \multirow{2}{*}{\(\uparrow\)} & \multirow{2}{*}{\(\uparrow\)} & \multirow{2}{*}{\(\uparrow\)} & \multirow{2}{*}{\(\uparrow\)} & \multirow{2}{*}{\(\uparrow\)} & \multirow{2}{*}{\(\uparrow\)} & \multirow{2}{*}{\(\uparrow\)} \\  & & & & & & & & & & & & \\ \hline \multirow{2}{*}{2-DG 6} & \multirow{2}{*}{–} & \multirow{2}{*}{–} & \multirow{2}{*}{–} & \multirow{2}{*}{–} & \multirow{2}{*}{Skr \(\downarrow\downarrow\)} & \multirow{2}{*}{–(\uparrow)} & Cont. 3\% & 1\% & & & & & & & & & & & & \\  & & & & & & & & 2-DG & 2-DG & 2-DG & & & & & & & & & \\ \hline FOG 7 [FOOTNOTE:7]Footnote 7: This is the case, the similar sign (\(\cdot\)) means uptake changed similar to binding 1.9’ ammonia Ri: 10 Mb, 83 HB: Hep-2 cells [164] 3. Did-the-1 phenyl-2d-demacyamino-morpholino-1-grouped: 1. 1 Mb, 24, HB-2 cells [164] 4. + 0.2-D Archaeology: 20 Mb, 24, HB-2 cells [165] 3. No or any minor effect on cytotoxicity by rich, chokera, or diphthe toxin. No effect on transfer endocytosis, Toxicity also shown for 32 in Hep-2, HMDL: 4, HMDL: 5-2 cells [173, 72] 3. This in table corresponds to HB-2 cells withThe reduction in Gb3 obtained with this treatment is too small to explain the very strong protection observed against these toxins, and most of this effect was due to a reduced transport from Golgi to the ER (Table 1). Thus, the increase in ether lipids might provide a protective effect against Shiga toxicity, although further studies are needed to understand the mechanisms behind this effect.