Annexin A6 regulates interleukin-2-mediated T-cell proliferation.

Annexin A6 (AnxA6) has been implicated in cell signalling by contributing to the organisation of the plasma membrane. Here we examined whether AnxA6 regulates signalling and proliferation in T cells. We used a contact hypersensitivity model to immune challenge wild-type (WT) and AnxA6(-/-) mice and found that the in vivo proliferation of CD4(+) T cells, but not CD8(+) T cells, was impaired in AnxA6(-/-) relative to WT mice. However, T-cell migration and signalling through the T-cell receptor ex vivo was similar between T cells isolated from AnxA6(-/-) and WT mice. In contrast, interleukin-2 (IL-2) signalling was reduced in AnxA6(-/-) compared with WT T cells. Further, AnxA6-deficient T cells had reduced membrane order and cholesterol levels. Taken together, our data suggest that AnxA6 regulates IL-2 homeostasis and sensitivity in T cells by sustaining a lipid raft-like membrane environment.

Human prefrontal cortex phospholipids containing docosahexaenoic acid increase during normal adult aging, whereas those containing arachidonic acid decrease.

Membrane phospholipids make up a substantial portion of the human brain, and changes in their amount and composition are thought to play a role in the pathogenesis of age-related neurodegenerative disease. Nevertheless, little is known about the changes that phospholipids undergo during normal adult aging. This study examined changes in phospholipid composition in the mitochondrial and microsomal membranes of human dorsolateral prefrontal cortex over the adult life span. The largest age-related changes were an increase in the abundance of both mitochondrial and microsomal phosphatidylserine 18:0_22:6 by approximately one-third from age 20 to 100 years and a 25% decrease in mitochondrial phosphatidylethanolamine 18:0_20:4. Generally, increases were seen with age in phospholipids containing docosahexaenoic acid across both membrane fractions, whereas phospholipids containing either arachidonic or adrenic acid decreased with age. These findings suggest a gradual change in membrane lipid composition over the adult life span.

Phospholipid peroxidation: lack of effect of fatty acid pairing.

Phospholipids where both fatty acids are polyunsaturated are very rare. Most organisms prefer to couple their polyunsaturated fatty acids (PUFA) with either a saturated (SAT) or a monounsaturated (MUFA) fatty acid. This study examined if these natural couplings are there to protect PUFA from themselves. Specifically, does the coupling of PUFA to SAT or MUFA reduce the potential for increased rates of peroxidation by shrouding these highly peroxidisable fatty acids with less peroxidisable fatty acids? The influence of head group was examined by using the two most common phospholipids found in vertebrate membranes i.e. phosphatidylcholine and phosphatidylethanolamine species. Fatty acid pairings included 16:0/18:2 versus 18:2/18:2 and 16:0/22:6 versus 22:6/22:6. All phospholipids were incorporated into liposomes that were matched for their total PUFA content i.e. 25% PUFA/PUFA or 50% SAT/PUFA with phosphatidylcholine 16:0/16:0 used as the background phospholipid. An iron initiator (Fe²âº/H2O2) was used to induce peroxidation and lipid hydroperoxide production was used to measure peroxidation. The results show that coupling of PUFA together on the same molecule does not increase peroxidation rates and therefore does not support the proposed hypothesis. The lower than expected levels of peroxidation measured for some phospholipid species (e.g. PtdEtn 22:6/22:6) is possibly due to the partitioning of these molecular species into the inner leaflet of the bilayer.