Midline crossing and Slit responsiveness of commissural axons require USP33

Yuasa-Kawada, Junichi; Kinoshita-Kawada, Mariko; Wu, Guan; Rao, Yi; Wu, Jane Y.

doi:10.1038/nn.2382

Cited by 54 publications

(64 citation statements)

References 15 publications

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“…Calsyntenin1 and RabGDI ensure membrane fusion of Robo1-containing Rab11-positive vesicles to the surface upon midline crossing. Studies using chick and mouse neurons also show that Robo1 is deubiquitylated by Usp33, leading to its stabilization on the cell surface and preventing its degradation on growing axons at appropriate time points (Yuasa-Kawada et al, 2009).…”

Section: The Spatiotemporal Gating Of Slit Responsiveness In Roboexprmentioning

confidence: 99%

Slit-Robo signaling

2016

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Slits are secreted proteins that bind to Roundabout (Robo) receptors. Slit-Robo signaling is best known for mediating axon repulsion in the developing nervous system. However, in recent years the functional repertoire of Slits and Robo has expanded tremendously and Slit-Robo signaling has been linked to roles in neurogenesis, angiogenesis and cancer progression among other processes. Likewise, our mechanistic understanding of Slit-Robo signaling has progressed enormously. Here, we summarize new insights into Slit-Robo evolutionary and system-dependent diversity, receptor-ligand interactions, signaling crosstalk and receptor activation.

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Section: The Spatiotemporal Gating Of Slit Responsiveness In Roboexprmentioning

confidence: 99%

Slit-Robo signaling

2016

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“…Development 137 (12) REVIEW Development 137 (12) and in vivo evidence that these two proteins interact (YuasaKawada et al, 2009a;Yuasa-Kawada et al, 2009b). The role of ubiquitin-mediated modification in regulating protein stability and function has been well established (Hershko and Ciechanover, 1998).…”

Section: Reviewmentioning

confidence: 99%

“…The role of ubiquitin-mediated modification in regulating protein stability and function has been well established (Hershko and Ciechanover, 1998). Upon examining the effect of Usp33 interaction with Robo, it was demonstrated that this de-ubiquitylating enzyme is required for the Slit-responsiveness of commissural neurons and of breast cancer cells (Yuasa-Kawada et al, 2009a;Yuasa-Kawada et al, 2009b). Usp33 mediates both of these functions by either preventing Robo1 from being targeted for degradation or by facilitating its endosomal recycling.…”

Section: Reviewmentioning

confidence: 99%

Moving away from the midline: new developments for Slit and Robo

2010

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SummaryIn most tissues, the precise control of cell migration and cellcell interaction is of paramount importance to the development of a functional structure. Several families of secreted molecules have been implicated in regulating these aspects of development, including the Slits and their Robo receptors. These proteins have well described roles in axon guidance but by influencing cell polarity and adhesion, they participate in many developmental processes in diverse cell types. We review recent progress in understanding both the molecular mechanisms that modulate Slit/Robo expression and their functions in neural and non-neural tissue. Key words: Axon guidance, Cell migration, Cell-cell interaction IntroductionIn most organisms, the central nervous system (CNS) develops along a bilateral axis of symmetry located at the midline (Placzek and Briscoe, 2005). During development, the ventral midline or floor plate acts as an organiser through the secretion of diffusible proteins (Placzek and Briscoe, 2005;Gore et al., 2008), which control the growth of axons and dendrites and the migration of neurons across the midline. In the forebrain, glial or neuronal cells delineate the midline (see Glossary, Box 1) and also control axon guidance. For more than two decades, many developmental neurobiologists have tried to understand the mechanisms that control midline crossing in the CNS and to answer some key questions. Firstly, how are commissural axons (see Glossary, Box 1) attracted to the midline and how do their growth cones (see Glossary, Box1) receive and integrate the multiple and contrasting signals released by midline cells? Secondly, what are the molecular and signalling changes that enable commissural axons to leave the midline and often to switch to a longitudinal growth mode? All midline-derived axon guidance factors are expressed at other locations in many developing and mature tissues, where they control a wide range of biological processes.Roundabout receptors (Robo) and their Slit ligands form one of the most crucial ligand-receptor pairings among the axon guidance molecules. Robos were identified in Drosophila in a mutant screen for genes that control the midline crossing of commissural axons (Kidd et al., 1998;Seeger et al., 1993). Similarly, Slit was discovered in Drosophila as a protein secreted by midline glia (Rothberg et al., 1988;Rothberg et al., 1990). Homologues of both proteins have since been discovered in many species (for a review, see . However, the Slit/Robo couple not only functions in axon guidance but also in a variety of developmental Development 137, 1939Development 137, -1952Development 137, (2010 Commissural axons Axons with cell bodies (somata) located on one side of the central nervous system (CNS) that project axons across the midline to contact target cells on the opposite side. Growth cone A specialised bulbous enlargement at the end of growing axons that is characterised by dynamic filamentous extensions, known as filopodia. They sense the environment and respond to adhesi...

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“…A very recent study implicated the ubiquitin-specific protease 33 (USP33) in Robo function 84 . Robo is destabilised in neurons when USP33 expression is knocked down by RNAi, and this USP33-mediated regulation of Robo is crucial for proper midline crossing of axons 84 .…”

Section: Regulation Of Axonal Guidance Cues By Ubiquitinationmentioning

confidence: 99%

“…Robo is destabilised in neurons when USP33 expression is knocked down by RNAi, and this USP33-mediated regulation of Robo is crucial for proper midline crossing of axons 84 . Considering that the UPS is not required for Slit-Robo signaling 85 , USP33-mediated deubiquitination may promote Robo signaling by preventing endocytosis and degradation, thereby maintaining the responsiveness of axons to Slit and thus avoiding aberrant midline crossing.…”

Section: Regulation Of Axonal Guidance Cues By Ubiquitinationmentioning

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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Midline crossing and Slit responsiveness of commissural axons require USP33

Cited by 54 publications

References 15 publications

Slit-Robo signaling

Slit-Robo signaling

Moving away from the midline: new developments for Slit and Robo

The role of ubiquitylation in nerve cell development

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