ATP-binding cassette transporter A7 (ABCA7) is expressed in the brain and has been detected in macrophages, microglia, and neurons. ABCA7 promotes efflux of lipids from cells to apolipoproteins and can also regulate phagocytosis and modulate processing of amyloid precursor protein (APP) to generate the Alzheimer's disease (AD) amyloid- (A) peptide. Genome-wide association studies have indicated that ABCA7 single nucleotide polymorphisms confer increased risk for late-onset AD; however, the role that ABCA7 plays in the brain in the AD context is unknown. In the present study, we crossed ABCA7-deficient (A7 Ϫ/Ϫ ) mice with J20 amyloidogenic mice to address this issue. We show that ABCA7 loss doubled insoluble A levels and thioflavine-S-positive plaques in the brain. This was not related to changes in APP processing (assessed by analysis of full-length APP and the APP  C-terminal fragment). Apolipoprotein E regulates cerebral A homeostasis and plaque load; however, the apolipoprotein E concentration was not altered by ABCA7 loss. Spatial reference memory was significantly impaired in both J20 and J20/A7 Ϫ/Ϫ mice compared with wild-type mice; however, there were no cognitive differences between J20 and J20/A7 Ϫ/Ϫ mice. There were also no major differences detected in hippocampal or plaqueassociated microglial/macrophage markers between J20 and J20/A7 Ϫ/Ϫ mice, whereas the capacity for bone marrow-derived macrophages derived from A7 Ϫ/Ϫ mice to take up oligomeric A was reduced by 51% compared with wild-type mice. Our results suggest that ABCA7 plays a role in the regulation of A homeostasis in the brain and that this may be related to altered phagocyte function.
Lipid rafts, defined as cholesterol-and sphingolipid-rich domains, provide specialized lipid environments understood to regulate the organization and function of many plasma membrane proteins. Growing evidence of their existence, protein cargo, and regulation is based largely on the study of isolated lipid rafts; however, the consistency and validity of common isolation methods is controversial. Here, we provide a detailed and direct comparison of the lipid and protein composition of plasma membrane "rafts" prepared from human macrophages by different methods, including several detergent-based isolations and a detergent-free method. We find that detergentbased and detergent-free methods can generate raft fractions with similar lipid contents and a biophysical structure close to that previously found on living cells, even in cells not expressing caveolin-1, such as primary human macrophages. However, important differences between isolation methods are demonstrated. Triton X-100-resistant rafts are less sensitive to cholesterol or sphingomyelin depletion than those prepared by detergent-free methods. Moreover, we show that detergent-based methods can scramble membrane lipids during the isolation process, reorganizing lipids previously in sonication-derived nonraft domains to generate new detergent-resistant rafts. The role of rafts in regulating the biological activities of macrophage plasma membrane proteins may require careful reevaluation using multiple isolation procedures, analyses of lipids, and microscopic techniques. Membranes of eukaryotic cells comprise an immense diversity of lipid species whose purpose and function are poorly understood. The simple model of biological membranes as two-dimensional lipid bilayers has recently been modified to recognize that the self-organizing properties of some lipids drive the formation of specialized domains within cellular membranes (1). Although biological membranes are typically in a fluid (liquid-disordered) state at physiological temperatures, cholesterol and sphingolipids self-associate to form condensed, liquid-ordered domains, or "lipid rafts," within the more fluid "sea" of the rest of the membrane (2-4).Recent interest in lipid rafts comes from the observation that some membrane proteins appear to preferentially partition into raft domains, whereas others are excluded from them. Hence, the structure of lipid rafts, their distribution, and their abundance could control key biological events dependent on the functional organization of the plasma membrane, such as signaling cascades (2), protein and lipid sorting and trafficking (5), cell adhesion and migration (6), entry of viruses (7), bacteria, and toxins (8), and immune responses (9). Lipid rafts have been implicated in a range of macrophage functions, including endotoxin-mediated activation and cytokine production, major histocompatibility complex (MHC) class II antigen presentation (10), phagocytosis (11), and cholesterol export (12). These cells are subject to large variations in cholesterol sta...
We sequenced the entire mitochondrial genome of Abispa ephippium (Hymenoptera: Vespoidea: Vespidae: Eumeninae) and most of the mitochondrial genome of Polistes humilis synoecus (Hymenoptera: Vespoidea: Vespidae: Polistinae). The arrangement of genes differed between the two genomes and also differed slightly from that inferred to be ancestral for the Hymenoptera. The genome organization for both vespids is different from that of all other mitochondrial genomes previously reported. A number of tRNA gene rearrangements were identified that represent potential synapomorphies for a subset of the Vespidae. Analysis of all available hymenopteran mitochondrial genome sequences recovered an uncontroversial phylogeny, one consistent with analyses of other types of data.
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