Acyl coenzyme A‐binding protein (ACBP) is phosphorylated and secreted by retinal Müller astrocytes following protein kinase C activation

Qian, Zuyuan; Bilderback, Timothy R.; Barmack, Neal H.

doi:10.1111/j.1471-4159.2008.05229.x

Cited by 26 publications

(32 citation statements)

References 65 publications

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“…Mammalian ACBP not only shuttles lipid intermediates around the cell but also serves as a precursor of DBI, a peptide that functions both in peripheral tissues and in the central nervous system (12,36). In the brain, DBI binds to GABA A receptors and modulates their response to GABA (12).…”

Section: Discussionmentioning

confidence: 99%

“…In the mammalian brain ACBP is also secreted and processed to generate a diazepam binding inhibitor (DBI) peptide that regulates ␥-aminobutyric acid A (GABA A ) ionotropic receptors in neurons (12). Qian and colleagues recently demonstrated the secretion of ACBP from Muller glial cells of the retina (36). In Dictyostelium discoideum the ACBP homolog AcbA is secreted and processed extracellularly into spore differentiation factor 2 (SDF-2), a 34-amino-acid peptide that is highly similar to DBI (2).…”

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confidence: 99%

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Unconventional Secretion of AcbA in Dictyostelium discoideum through a Vesicular Intermediate

et al. 2010

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The acyl coenzyme A (CoA) binding protein AcbA is secreted unconventionally and processed into spore differentiation factor 2 (SDF-2), a peptide that coordinates sporulation in Dictyostelium discoideum. We report that AcbA is localized in vesicles that accumulate in the cortex of prespore cells just prior to sporulation. These vesicles are not observed after cells are stimulated to release AcbA but remain visible after stimulation in cells lacking the Golgi reassembly stacking protein (GRASP). Acyl-CoA binding is required for the inclusion of AcbA in these vesicles, and the secretion of AcbA requires N-ethylmaleimide-sensitive factor (NSF). About 1% of the total cellular AcbA can be purified within membrane-bound vesicles. The yield of vesicles decreases dramatically when purified from wild-type cells that were stimulated to release AcbA, whereas the yield from GRASP mutant cells was only modestly altered by stimulation. We suggest that these AcbA-containing vesicles are secretion intermediates and that GRASP functions at a late step leading to the docking/fusion of these vesicles at the cell surface.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Unconventional Secretion of AcbA in Dictyostelium discoideum through a Vesicular Intermediate

et al. 2010

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“…Microglia were cultured from retinas of C57BL/6 mice at postnatal day 10 -30 (P10 -P30) as described previously (Ma et al, 2009). Enucleated globes were incubated in HBSS buffer containing 2% dispase (Roche) at 37°C for 45-60 min and then rinsed three times with DMEM containing 10% fetal bovine serum (FBS; Invitrogen).…”

Section: Experimental Animals Heterozygous Cx3cr1mentioning

confidence: 99%

“…Primary endogenous ligands to TSPO include a polypeptide called diazepam-binding inhibitor (DBI) and its shorter peptide cleavage products called endozepines (Ferrero et al, 1986). These molecules, expressed and secreted by macroglial populations in the CNS (Yanase et al, 2002), bind TSPO with high affinity (Guidotti et al, 1983;Slobodyansky et al, 1989), stimulating steroidogenesis (Papadopoulos et al, 1991;Do-Rego et al, 1998). Although DBI has been linked to Alzheimer's disease , its functional significance with regard to TSPO signaling is unknown.…”

Section: Introductionmentioning

confidence: 99%

Macroglia-Microglia Interactions via TSPO Signaling Regulates Microglial Activation in the Mouse Retina

Wang¹,

Wang²,

Zhao³

et al. 2014

J. Neurosci.

188

164

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Chronic retinal inflammation in the form of activated microglia and macrophages are implicated in the etiology of neurodegenerative diseases of the retina, including age-related macular degeneration, diabetic retinopathy, and glaucoma. However, molecular biomarkers and targeted therapies for immune cell activation in these disorders are currently lacking. To address this, we investigated the involvement and role of translocator protein (TSPO), a biomarker of microglial and astrocyte gliosis in brain degeneration, in the context of retinal inflammation. Here, we find that TSPO is acutely and specifically upregulated in retinal microglia in separate mouse models of retinal inflammation and injury. Concomitantly, its endogenous ligand, diazepam-binding inhibitor (DBI), is upregulated in the macroglia of the mouse retina such as astrocytes and Müller cells. In addition, we discover that TSPO-mediated signaling in microglia via DBI-derived ligands negatively regulates features of microglial activation, including reactive oxygen species production, TNF-␣ expression and secretion, and microglial proliferation. The inducibility and effects of DBI-TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence. Our results indicate that TSPO is a promising molecular marker for imaging inflammatory cell activation in the retina and highlight DBI-TSPO signaling as a potential target for immodulatory therapies.

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“…Among higher eukaryotes, there are multiple copies of Acbp-encoding genes in one genome, and these proteins differ in size and subcellular localization (28)(29)(30)(31)(32)(33)(34). Nonetheless, all Acbps are conserved in the acyl-CoA-binding domain (34).…”

mentioning

confidence: 99%

Secreted Acb1 Contributes to the Yeast-to-Hypha Transition in Cryptococcus neoformans

Zhao

Kirkman

et al. 2016

Appl Environ Microbiol

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Adaptation to stress by eukaryotic pathogens is often accompanied by a transition in cellular morphology. The human fungal pathogen Cryptococcus neoformans is known to switch between the yeast and the filamentous form in response to amoebic predation or during mating. As in the classic dimorphic fungal pathogens, the morphotype is associated with the ability of cryptococci to infect various hosts. Many cryptococcal factors and environmental stimuli, including pheromones (small peptides) and nutrient limitation, are known to induce the yeast-to-hypha transition. We recently discovered that secreted matricellular proteins could also act as intercellular signals to promote the yeast-to-hypha transition. Here we show that the secreted acyl coenzyme A (acyl-CoA)-binding protein Acb1 plays an important role in enhancing this morphotype transition. Acb1 does not possess a signal peptide. Its extracellular secretion and, consequently, its function in filamentation are dependent on an unconventional GRASP (Golgi reassembly stacking protein)-dependent secretion pathway. Surprisingly, intracellular recruitment of Acb1 to the secretory vesicles is independent of Grasp. In addition to Acb1, Grasp possibly controls the secretion of other cargos, because the grasp⌬ mutant, but not the acb1⌬ mutant, is defective in capsule production and macrophage phagocytosis. Nonetheless, Acb1 is likely the major or the sole effector of Grasp in terms of filamentation. Furthermore, we found that the key residue of Acb1 for acyl binding, Y80, is critical for the proper subcellular localization and secretion of Acb1 and for cryptococcal morphogenesis.A daptation to a changing environment by eukaryotic microbes is often accompanied by a transition in cellular morphology. The human fungal pathogen Cryptococcus neoformans causes devastating cryptococcal meningitis, which claims the lives of hundreds of thousands of people each year (1). Late diagnosis, limited options for antifungals, and the lack of vaccines to prevent cryptococcosis all contribute to the high mortality rate of this disease (2). C. neoformans typically grows as yeasts but can switch from yeasts to filaments (hyphae or pseudohyphae) in response to predation (e.g., by amoebae) or during sexual reproduction (3-7). As with many other fungal pathogens, the morphotype of C. neoformans shapes its interactions with various hosts (8). As we demonstrated recently, the hyphal form is associated with the attenuation of virulence in mouse models of cryptococcosis, because the hyphal morphotype elicits strong and protective host immune responses (9, 10). On the other hand, the hyphal morphotype assists the fungus in resisting predation from soil amoebae (8), increases its ability to explore the environment (11), and is linked to its unisexual and bisexual reproduction (3,(12)(13)(14). Thus, it is important to understand the factors that promote cryptococcal hyphal growth.Many environmental stimuli and a few cryptococcal factors that promote hyphal growth in C. neoformans have been identified ...

show abstract

Acyl coenzyme A‐binding protein (ACBP) is phosphorylated and secreted by retinal Müller astrocytes following protein kinase C activation

Cited by 26 publications

References 65 publications

Unconventional Secretion of AcbA in Dictyostelium discoideum through a Vesicular Intermediate

Unconventional Secretion of AcbA in Dictyostelium discoideum through a Vesicular Intermediate

Macroglia-Microglia Interactions via TSPO Signaling Regulates Microglial Activation in the Mouse Retina

Secreted Acb1 Contributes to the Yeast-to-Hypha Transition in Cryptococcus neoformans

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