E3 Ligase Nedd4 Promotes Axon Branching by Downregulating PTEN

Drinjákovic, Jována; Jung, Hosung; Campbell, Douglas S.; Strochlic, Laure; Dwivedy, Asha; Holt, Christine E.

doi:10.1016/j.neuron.2010.01.017

Cited by 183 publications

(187 citation statements)

References 77 publications

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“…The regulation of a subset of substrates must be coordinated to balance parallel regulatory pathways in neuronal differentiation or development. For example, Nedd4-1 ubiquitinates and thereby regulates Rap2 during dendrite development 97 and may, at the same time, control axon branching by ubiquitinating PTEN 98 . It is obvious that such regulatory pathways must be properly adjusted in order to achieve proper neuronal network formation.…”

Section: Discussionmentioning

confidence: 99%

The role of ubiquitylation in nerve cell development

2011

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| Nerve cell development in the brain is a tightly regulated process. The generation of neurons from precursor cells, their migration to the appropriate target sites, their extensive arborisation, and their integration into functional networks through synapse formation and refinement are governed by multiple interdependent signaling cascades. The function and turnover of proteins involved in these signaling cascades, in turn, are spatially and temporally controlled by ubiquitination. Recent advances have provided first insights into the highly complex and intricate molecular pathways that regulate ubiquitination during all stages of neural development and operate in parallel with other regulatory processes such as phosphorylation or cyclic nucleotide signaling.

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Section: Discussionmentioning

confidence: 99%

The role of ubiquitylation in nerve cell development

2011

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“…Antisense morpholino oligomers were diluted to a concentration of 1 mM. The xDicer-MO and Pten-MO have been previously published (11,36). The Ins-MO and Igf2-MO were tested using GFP fusion protein constructs (Fig.…”

Section: Methodsmentioning

confidence: 99%

MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1 activity in the size control of the Xenopus kidney

Romaker

Kumar

Cerqueira

et al. 2014

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

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Significance The kidney is an essential organ to remove metabolic waste products and retain essential nutrients. To successfully execute these processes, the kidney and its functional unit, the nephron, must be correctly proportioned. Surprisingly, little is known about the processes governing kidney size. Here, we use the amphibian pronephric kidney as a paradigm to study the molecular mechanisms regulating size control. We show for the first time, to our knowledge, that growth factors belonging to the Insulin growth factor family are critically important in establishing kidney size. Moreover, we demonstrate that the strength of the signal is dependent on the presence of small noncoding RNAs termed microRNAs. These provide robustness to size control and ascertain that the kidney develops properly.

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“…Interestingly, Calpain is also expressed in the Xenopus spinal cord and its activity is regulated by calcium transients . It has also recently been shown that Nedd4, an E3 ubiquitin ligase, is necessary to turn off PTEN, causing an increase in PI3K signalling and inducing axon branching in Xenopus retinal ganglion cells (Drinjakovic et al, 2010). In a concomitant paper, the knockout of Nedd4-1 in mice showed that Nedd4 is necessary for dendrite arborisation and neurite growth (Kawabe et al, 2010).…”

Section: Research Articlementioning

confidence: 99%

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

et al. 2010

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SUMMARYDuring development, many organs, including the kidney, lung and mammary gland, need to branch in a regulated manner to be functional. Multicellular branching involves changes in cell shape, proliferation and migration. Axonal branching, however, is a unicellular process that is mediated by changes in cell shape alone and as such appears very different to multicellular branching. Sprouty (Spry) family members are well-characterised negative regulators of Receptor tyrosine kinase (RTK) signalling. Knockout of Spry1, 2 and 4 in mouse result in branching defects in different organs, indicating an important role of RTK signalling in controlling branching pattern. We report here that Spry3, a previously uncharacterised member of the Spry family plays a role in axonal branching. We found that spry3 is expressed specifically in the trigeminal nerve and in spinal motor and sensory neurons in a Brain-derived neurotrophin factor (BDNF)-dependent manner. Knockdown of Spry3 expression causes an excess of axonal branching in spinal cord motoneurons in vivo. Furthermore, Spry3 inhibits the ability of BDNF to induce filopodia in Xenopus spinal cord neurons. Biochemically, we show that Spry3 represses calcium release downstream of BDNF signalling. Altogether, we have found that Spry3 plays an important role in the regulation of axonal branching of motoneurons in vivo, raising the possibility of unexpected conservation in the involvement of intracellular regulators of RTK signalling in multicellular and unicellular branching.

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E3 Ligase Nedd4 Promotes Axon Branching by Downregulating PTEN

Cited by 183 publications

References 77 publications

The role of ubiquitylation in nerve cell development

The role of ubiquitylation in nerve cell development

MicroRNAs are critical regulators of tuberous sclerosis complex and mTORC1 activity in the size control of the Xenopus kidney

Characterisation of a new regulator of BDNF signalling, Sprouty3, involved in axonal morphogenesis in vivo

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