Pathophysiology of Human Genetic CD36 Deficiency

Hirano, Ken‐ichi; Kuwasako, Takahiro; Nakagawa-Toyama, Yumiko; Janabi, Mohamed; Yamashita, Shizuya; Matsuzawa, Yūji

doi:10.1016/s1050-1738(03)00026-4

Cited by 129 publications

(92 citation statements)

References 59 publications

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“…The uptake of free fatty acids can be mediated in a large number of cells by the fatty acid transporter (FAT), also referred to as CD36. CD36 has been previously associated with insulin resistance (93) and atherosclerotic cardiovascular diseases (94). We therefore analyzed the expression level of CD36 in hTDP-43…”

Section: A315tmentioning

confidence: 99%

Mitochondrial Dysfunction and Decrease in Body Weight of a Transgenic Knock-in Mouse Model for TDP-43

Stribl

Samara

Trümbach

et al. 2014

Journal of Biological Chemistry

104

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Background: Mutations in TDP-43 are frequently found in ALS patients. Results: A315T TDP-43 protein is elevated from this transgenic knock-in allele due to disturbed feedback regulation. Conclusion: Elevation of A315T TDP-43 was insufficient to cause ALS in this mutant. Significance: This TDP-43 allele could be valuable in determining genetic or environmental factors that cause full-blown FTLD or ALS.

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Section: A315tmentioning

confidence: 99%

Mitochondrial Dysfunction and Decrease in Body Weight of a Transgenic Knock-in Mouse Model for TDP-43

Stribl

Samara

Trümbach

et al. 2014

Journal of Biological Chemistry

104

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“…In vertebrates, CD36 is an 88-kDa integral membrane protein receptor that mediates internalization of oxidized low-density lipoprotein by macrophages (16), formation of atherosclerotic plaques (17), and the import of long-chain fatty acids by adipose, heart, and other tissues (18,19). In humans, loss of CD36 is linked to a wide range of disorders including insulin resistance, dyslipidemia, and atherosclerosis (17,18,(20)(21)(22). CD36 molecules share a common domain structure with short intracellular domains at the N and C termini, two membrane spanning domains, and a large extracellular domain (19).…”

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confidence: 99%

SNMP is a signaling component required for pheromone sensitivity in Drosophila

Jin

Smith³

2008

Proc. Natl. Acad. Sci. U.S.A.

263

277

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The only known volatile pheromone in Drosophila, 11-cis-vaccenyl acetate (cVA), mediates a variety of behaviors including aggregation, mate recognition, and sexual behavior. cVA is detected by a small set of olfactory neurons located in T1 trichoid sensilla on the antennae of males and females. Two components known to be required for cVA reception are the odorant receptor Or67d and the extracellular pheromone-binding protein LUSH. Using a genetic screen for cVA-insensitive mutants, we have identified a third component required for cVA reception: sensory neuron membrane protein (SNMP). SNMP is a homolog of CD36, a scavenger receptor important for lipoprotein binding and uptake of cholesterol and lipids in vertebrates. In humans, loss of CD36 is linked to a wide range of disorders including insulin resistance, dyslipidemia, and atherosclerosis, but how CD36 functions in lipid transport and signal transduction is poorly understood. We show that SNMP is required in pheromone-sensitive neurons for cVA sensitivity but is not required for sensitivity to general odorants. Using antiserum to SNMP infused directly into the sensillum lymph, we show that SNMP function is required on the dendrites of cVA-sensitive neurons; this finding is consistent with a direct role in cVA signal transduction. Therefore, pheromone perception in Drosophila should serve as an excellent model to elucidate the role of CD36 members in transmembrane signaling.CD36 ͉ olfaction ͉ olfactory ͉ sexual behavior ͉ signal transduction C VA (11-cis-vaccenyl acetate) mediates social behaviors in Drosophila, and its reception requires the odorant receptor Or67d and the extracellular pheromone-binding protein LUSH (1-4). Misexpression of Or67d receptors in trichoid neurons that are normally insensitive to pheromone confers cVA sensitivity but only if LUSH is present (3). However, Or67d and LUSH are not sufficient to confer cVA sensitivity to basiconic neurons (T.S.H. and D.P.S., unpublished work). This finding reveals that there are additional factors required for cVA sensitivity present in trichoid sensilla that are lacking in basiconic sensilla. Using a genetic screen, we set out to identify additional components important for cVA sensitivity. We screened Ϸ3,000 mutagenized third-chromosome lines selected for homozygous viability (5). We screened each mutant line for T1 electrophysiological responses to cVA using single sensillum electrophysiological recordings (2, 3, 6). We identified five complementation groups that were cVA-insensitive yet retained spontaneous activity in the pheromone-sensing neurons (the vains phenotype) ( Fig. 1 and Table 1). The presence of spontaneous activity indicates that the neurons are present, are viable, and can sustain action potentials, thereby eliminating nonspecific mutants affecting development or general neuronal function. Of the five complementation groups recovered, two, Or67d and Or83b, affect genes previously implicated in cVA or general odorant detection, two remain unmapped, and the fifth encodes SNMP, a new cVA...

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“…It is unknown whether CD36 deficiency influences myocardial Ca 2؉ handling and phospholipid metabolism, which could compromise the heart, typically during stresses. Myocardial function was examined in fed or fasted (18 - The membrane fatty acid (FA) 2 translocase (FAT/CD36) is abundant in the heart (1) and plays an important role in facilitating myocardial uptake of circulating unesterified FA in mice (2-4) as well as humans (5,6). The importance of CD36 in lipid metabolism and the associated cardiovascular risk are supported by recent genetic studies.…”

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confidence: 99%