scholarly journals Role of Drosophila Rap/Fzr (DCdh1) in Retinal Axon Targeting and its Interactions with Loco and Liprin-alpha

2020 ◽  
Author(s):  
Marta Grońska-Pęski ◽  
Tadmiri R. Venkatesh

AbstractThe development of the wild type Drosophila compound eye involves stereotypical targeting of photoreceptor axons to the specific layers of the optic ganglion, medulla and lamina, in the third instar larvae. To test the hypothesis that ubiquitin ligases play an important role during retinal axon targeting we have examined the patterns of axon targeting in the developing eye of the retina aberrant in pattern (rap/fzr) mutants. Rap/Fzr is a homolog of mammalian Cdh1, an activator of anaphase promoting complex (APC), a multi-subunit E3 ubiquitin ligase, regulating the cell cycle progression. Previous work has shown that Rap/Fzr is required during eye development for proper cell cycle regulation, glia differentiation and pattern formation. It was also necessary for proper neuromuscular junction development and circadian rhythms. Our results show that Rap/Fzr is required for proper retinal axon targeting in the developing eye. Using ro-tau-lacZ, we show that the R2-R5 axons fail to stop in the lamina and mis-target to the medulla levels. Also, mosaic analyses experiments using FLP-FRT and GAL4-UAS techniques show that Rap/Fzr functions in a cell autonomous manner. To test for possible role of other signalling molecules and interactions with Rap/Fzr, we have examined rap/fzr axon projection phenotypes in double mutant combinations with the RGS protein, locomotion defective (loco) mutants and a scaffolding protein, Liprin-α. Our studies suggest that Rap/Fzr is required for proper axon targeting during Drosophila visual system development, and the phenotype is enhanced in double mutants with either loco or Liprin-α. These results are consistent with other mammalian studies reporting a role of Cdh1 in axon growth and targeting and provides further insights into neuronal functions of the ubiquitin ligase APC/CCdh1.HighlightsLoss of rap/fzr in the third instar Drosophila eye disc leads to photoreceptor axon overgrowthOverexpression of rap/fzr leads to photoreceptor axon leads to axon shortening and clumpingLoss of LocoP452 leads to photoreceptor overgrowthDouble mutants of rap and loco or rap and Liprin-α show axon enhancement of the axon targeting defects in the Drosophila third instar larvae eye imaginal discs.

Author(s):  
Jiayan Xie ◽  
Yimei Jin ◽  
Guang Wang

AbstractAs the largest family of E3 ligases, the Skp1-cullin 1-F-box (SCF) E3 ligase complex is comprised of Cullins, Skp1 and F-box proteins. And the SCF E3 ubiquitin ligases play an important role in regulating critical cellular processes, which promote degradation of many cellular proteins, including signal transducers, cell cycle regulators, and transcription factors. We review the biological roles of the SCF ubiquitin-ligase complex in gametogenesis, oocyte-to-embryo transition, embryo development and the regulation for estrogen and progestin. We find that researches about the SCF ubiquitin-ligase complex at the beginning of life are not comprehensive, thus more in-depth researches will promote its eventual clinical application.


2007 ◽  
Vol 306 (1) ◽  
pp. 371-372
Author(s):  
Tania Moin ◽  
Margarita Kaplow ◽  
Eliana Mino ◽  
Tadmiri Venkatesh

1995 ◽  
Vol 12 (2) ◽  
pp. 85-93 ◽  
Author(s):  
Hidehiko Ogawa ◽  
Tadashi Mori ◽  
Hiroshi Shimizu

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89195 ◽  
Author(s):  
Francine C. A. Gérard ◽  
Ruifeng Yang ◽  
Bizhan Romani ◽  
Alexis Poisson ◽  
Jean-Philippe Belzile ◽  
...  

Oncogene ◽  
2021 ◽  
Author(s):  
Eleonora Ottina ◽  
Veera Panova ◽  
Laura Doglio ◽  
Anastasiya Kazachenka ◽  
Georgina Cornish ◽  
...  

AbstractThe ubiquitin-proteasome system maintains protein homoeostasis, underpins the cell cycle, and is dysregulated in cancer. However, the role of individual E3 ubiquitin ligases, which mediate the final step in ubiquitin-mediated proteolysis, remains incompletely understood. Identified through screening for cancer-specific endogenous retroviral transcripts, we show that the little-studied E3 ubiquitin ligase HECTD2 exerts dominant control of tumour progression in melanoma. HECTD2 cell autonomously drives the proliferation of human and murine melanoma cells by accelerating the cell cycle. HECTD2 additionally regulates cancer cell production of immune mediators, initiating multiple immune suppressive pathways, which include the cyclooxygenase 2 (COX2) pathway. Accordingly, higher HECTD2 expression is associated with weaker anti-tumour immunity and unfavourable outcome of PD-1 blockade in human melanoma and counteracts immunity against a model tumour antigen in murine melanoma. This central, multifaceted role of HECTD2 in cancer cell-autonomous proliferation and in immune evasion may provide a single target for a multipronged therapy of melanoma.


2012 ◽  
Vol 2 (1) ◽  
pp. 2 ◽  
Author(s):  
Yasir Hasan Siddique

In the present study the effects of curcumin was studied against the toxic effects induced by 0.025 and 0.050 ml/ml of cyclophosphamide (CP) in the third instar larvae of transgenic <em>Drosophila melanogaster (hsp70-lacZ)Bg9</em> using hsp70 expression and dye exclusion test as a parameter. The exposure of the third instar larvae to 0.025ml/ml of CP along with 1, 5 and 10 mg/ml of curcumin results in the dose dependent significant decrease in the <em>hsp70</em> expression and tissue damage for 12, 24 and 48hr of duration. Similar results were obtained with the exposure of third instar larvae to 0.050 ml/ml of CP along with 1, 5 and 10 mg/ml of curcumin. The selected doses of curcumin i.e. 1, 5 and 10 mg/ml were not toxic but reduced significantly the expression of <em>hsp70</em> and tissue damage induced by CP. The results of the present study suggest that the curcumin has a protective role against the toxic effects of CP in the third instar larvae of transgenic <em>Drosophila melanogaster (hsp70-lacZ)Bg9</em>.


2005 ◽  
Vol 25 (21) ◽  
pp. 9292-9303 ◽  
Author(s):  
Taichi Hara ◽  
Takumi Kamura ◽  
Shuhei Kotoshiba ◽  
Hidehisa Takahashi ◽  
Kenichiro Fujiwara ◽  
...  

ABSTRACT KPC2 (Kip1 ubiquitylation-promoting complex 2) together with KPC1 forms the ubiquitin ligase KPC, which regulates degradation of the cyclin-dependent kinase inhibitor p27 at the G1 phase of the cell cycle. KPC2 contains a ubiquitin-like (UBL) domain, two ubiquitin-associated (UBA) domains, and a heat shock chaperonin-binding (STI1) domain. We now show that KPC2 interacts with KPC1 through its UBL domain, with the 26S proteasome through its UBL and NH2-terminal UBA domains, and with polyubiquitylated proteins through its UBA domains. The association of KPC2 with KPC1 was found to stabilize KPC1 in a manner dependent on the STI1 domain of KPC2. KPC2 mutants that lacked either the NH2-terminal or the COOH-terminal UBA domain supported the polyubiquitylation of p27 in vitro, whereas a KPC2 derivative lacking the STI1 domain was greatly impaired in this regard. Depletion of KPC2 by RNA interference resulted in inhibition of p27 degradation at the G1 phase, and introduction of KPC2 derivatives into the KPC2-depleted cells revealed that the NH2-terminal UBA domain of KPC2 is essential for p27 degradation. These observations suggest that KPC2 cooperatively regulates p27 degradation with KPC1 and that the STI1 domain as well as the UBL and UBA domains of KPC2 are indispensable for its function.


2017 ◽  
Vol 292 (35) ◽  
pp. 14311-14324 ◽  
Author(s):  
Taner Dogan ◽  
Florian Gnad ◽  
Jocelyn Chan ◽  
Lilian Phu ◽  
Amy Young ◽  
...  

2010 ◽  
Vol 12 (1-2) ◽  
pp. 313-282
Author(s):  
ʿAbd al-ʿAzīz Mūsā
Keyword(s):  

This article sheds light on the role of grammar in understanding legislative texts, with reference to the wuḍūʾ verse (Q. 5:6). The first section deals with the issue of washing the elbows along with the feet as part of ritual ablution, and lists the various interpretations of the preposition ilā in the aya, and discusses the grammatical theory used by different fuqahāʾ to support their arguments. The second section tackles how much of the head should be rubbed in ritual ablution, with regard to the use of the preposition bi- in the phrase bi-ruʾūsikum, while the third focuses on the two readings of the phrase arjulakum/arjulikum (‘your feet’) and on passing legislative judgement on whether the feet be washed or just rubbed. The study concludes that lugha and fiqh theory are of mutual importance and together help to clarify legislative judgements, and, on this basis, that jurists should not pass any legislative judgement without referring to language.


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