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Identification of putative endocannabinoid N-acyltransferases in C. elegans
Title
Identification of putative endocannabinoid N-acyltransferases in C. elegans.
Creator
Armesto, Jose, Reis-Rodrigues, Pedro, Lone, Museer A., Gill, Matthew S.
Abstract/Description
The N-acyltransferase enzyme (NAT) is responsible for synthesizing N-acyl-phospatidylethanolamines which is the first step in the synthesis of N-acylethanolamines, an important class of lipids that are used by the endocannabinoid system as signaling molecules. A calcium dependent NAT enzyme has been characterized biochemically but has not been cloned. The purpose of this study was to identify NAT enzyme in Caenorhabditis elegans. The strain MGL107 overproduces NAEs and as a result exhibits...
Show moreThe N-acyltransferase enzyme (NAT) is responsible for synthesizing N-acyl-phospatidylethanolamines which is the first step in the synthesis of N-acylethanolamines, an important class of lipids that are used by the endocannabinoid system as signaling molecules. A calcium dependent NAT enzyme has been characterized biochemically but has not been cloned. The purpose of this study was to identify NAT enzyme in Caenorhabditis elegans. The strain MGL107 overproduces NAEs and as a result exhibits delayed growth. We have found that 10 of 35 genes with N-acyltransferase activity are able to restore growth of MGL107. Interestingly, acl-10, acl-12, and acl-13 also showed increased mRNA levels in a strain with reduced NAEs, possibly indicating a compensatory mechanism. These data suggests that these three genes could potentially code for the calcium dependent NAT and should be further analyzed biochemically.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA0005001
Subject Headings
College students --Research --United States.
Format
Document (PDF)
Aberrant Autolysosomal Regulation Is Linked to The Induction of Embryonic Senescence: Differential Roles of Beclin 1 and p53 in Vertebrate Spns1 Deficien
Title
Aberrant Autolysosomal Regulation Is Linked to The Induction of Embryonic Senescence: Differential Roles of Beclin 1 and p53 in Vertebrate Spns1 Deficien.
Creator
Tomoyuki Sasaki, Shanshan Lian, Jie Qi, Peter E. Bayliss, Christopher E. Carr, Jennifer L. Johnson, Sujay Guha, Patrick Kobler, Sergio D. Catz, Matthew Gill, Kailiang Jia, Daniel J. Klionsky
Abstract/Description
Spinster (Spin) in Drosophila or Spinster homolog 1 (Spns1) in vertebrates is a putative lysosomal H+-carbohydrate transporter, which functions at a late stage of autophagy. The Spin/Spns1 defect induces aberrant autolysosome formation that leads to embryonic senescence and accelerated aging symptoms, but little is known about the mechanisms leading to the pathogenesis in vivo. Beclin 1 and p53 are two pivotal tumor suppressors that are critically involved in the autophagic process and its...
Show moreSpinster (Spin) in Drosophila or Spinster homolog 1 (Spns1) in vertebrates is a putative lysosomal H+-carbohydrate transporter, which functions at a late stage of autophagy. The Spin/Spns1 defect induces aberrant autolysosome formation that leads to embryonic senescence and accelerated aging symptoms, but little is known about the mechanisms leading to the pathogenesis in vivo. Beclin 1 and p53 are two pivotal tumor suppressors that are critically involved in the autophagic process and its regulation. Using zebrafish as a genetic model, we show that Beclin 1 suppression ameliorates Spns1 lossmediated senescence as well as autophagic impairment, whereas unexpectedly p53 deficit exacerbates both of these characteristics. We demonstrate that ‘basal p53’ activity plays a certain protective role(s) against the Spns1 defect-induced senescence via suppressing autophagy, lysosomal biogenesis, and subsequent autolysosomal formation and maturation, and that p53 loss can counteract the effect of Beclin 1 suppression to rescue the Spns1 defect. By contrast, in response to DNA damage, ‘activated p53’ showed an apparent enhancement of the Spns1-deficient phenotype, by inducing both autophagy and apoptosis. Moreover, we found that a chemical and genetic blockage of lysosomal acidification and biogenesis mediated by the vacuolar-type H+-ATPase, as well as of subsequent autophagosome-lysosome fusion, prevents the appearance of the hallmarks caused by the Spns1 deficiency, irrespective of the basal p53 state. Thus, these results provide evidence that Spns1 operates during autophagy and senescence differentially with Beclin 1 and p53.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FAUIR000526
Format
Document (PDF)