Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/β-catenin signaling

Berndt, Jason D.; Aoyagi, Atsushi; Yang, Peter; Anastas, Jamie N.; Tang, Lan; Moon, Randall T.

doi:10.1083/jcb.201107021

Cited by 92 publications

(126 citation statements)

References 47 publications

(85 reference statements)

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“…One somewhat unexpected result is the number of Wnt pathway members that may interact with Mib1. As mentioned previously, Mib1 had been shown to interact with one Wnt pathway member, RYK (18). Our study enlarged on this, producing a range of powerful Wnt pathway interaction partners that includes several members of the Catenin family (alpha, beta, delta1, and delta2), several MAP/microtubule affinity-regulating kinases (Mark1, 3, and 4), and Casein kinase family members.…”

Section: Discussionmentioning

confidence: 96%

“…Its critical regulation of NotchDelta signaling alone incorporates it into almost every aspect of nervous system development (6,10,(55)(56)(57)(58)(59)(60). More recently, an interactome study revealed that it also plays a role in the equally vital Wnt signaling pathway (18). Furthermore, several other potent developmental modulators beyond these key pathways have also been revealed to interact with Mib1, such as SMN1 (17) and the CDK5/p35 complex (12).…”

Section: Discussionmentioning

confidence: 99%

“…Mib1 was found to mediate the degradation of survival motor neuron 1 (SMN1), which contributes to spinal muscular atrophy (17). Mib1 was reported to be essential for Wnt3A activation of beta-catenin signaling through the receptor RYK (18), and a recent yeast two-hybrid screen indicated that Mib1 interacts with 81 candidate proteins beyond the canonical Notch pathway (19). The ongoing identification of new Mib1 interaction partners and functions underscores the need to characterize the Mib1 interactome en masse with high confidence.…”

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confidence: 99%

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Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth

Mertz¹,

Tan

Pagala

et al. 2015

Molecular & Cellular Proteomics

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The mind bomb 1 (Mib1) ubiquitin ligase is essential for controlling metazoan development by Notch signaling and possibly the Wnt pathway. It is also expressed in postmitotic neurons and regulates neuronal morphogenesis and synaptic activity by mechanisms that are largely unknown. We sought to comprehensively characterize the Mib1 interactome and study its potential function in neuron development utilizing a novel sequential elution strategy for affinity purification, in which Mib1 binding proteins were eluted under different stringency and then quantified by the isobaric labeling method. The strategy identified the Mib1 interactome with both deep coverage and the ability to distinguish high-affinity partners from low-affinity partners. A total of 817 proteins were identified during the Mib1 affinity purification, including 56 high-affinity partners and 335 low-affinity partners, whereas the remaining 426 proteins are likely copurified contaminants or extremely weak binding proteins. The analysis detected all previously known Mib1-interacting proteins and revealed a large number of novel components involved in Notch and Wnt pathways, endocytosis and vesicle transport, the ubiquitin-proteasome system, cellular morphogenesis, and synaptic activities. Immunofluorescence studies further showed colocalization of Mib1 with five selected proteins: the Usp9x (FAM) deubiquitinating enzyme, alpha-, beta-, and delta-catenins, and CDKL5. Mutations of CDKL5 are associated with early infantile epileptic encephalopathy-2 (EIEE2), a severe form of mental retardation. We found that the expression of Mib1 downregulated the protein level of CDKL5 by ubiquitination, and antagonized CDKL5 function during the formation of dendritic spines. Thus, the sequential elution strategy enables biochemical characterization of protein interac-

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth

Mertz¹,

Tan

Pagala

et al. 2015

Molecular & Cellular Proteomics

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“…Only trace amounts of wild-type Flag-Mib1 could be coimmunoprecipitated with Myc-Plk4 but, remarkably, strong binding was seen between Plk4 and a Flag-Mib1DRING mutant (Fig. 1C,D), which is catalytically inactive (Berndt et al, 2011;Itoh et al, 2003). Myc-Cep135, analyzed as a control, was unable to bind either wild-type or mutant Mib1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis

Čajánek

Glatter

Nigg

2015

Journal of Cell Science

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BSTRACTCentrioles function as core components of centrosomes and as basal bodies for the formation of cilia and flagella. Thus, effective control of centriole numbers is essential for embryogenesis, tissue homeostasis and genome stability. In mammalian cells, the centriole duplication cycle is governed by Polo-like kinase 4 (Plk4). Here, we identify the E3 ubiquitin ligase Mind bomb (Mib1) as a new interaction partner of Plk4. We show that Mib1 localizes to centriolar satellites but redistributes to centrioles in response to conditions that induce centriole amplification. The E3 ligase activity of Mib1 triggers ubiquitylation of Plk4 on multiple sites, causing the formation of Lys11-, Lys29-and Lys48-ubiquitin linkages. These modifications control the abundance of Plk4 and its ability to interact with centrosomal proteins, thus counteracting centriole amplification induced by excess Plk4. Collectively, these results identify the interaction between Mib1 and Plk4 as a new and important element in the control of centriole homeostasis.

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“…Indeed, Wnt5a/Ryk-mediated axon outgrowth and chemorepulsion have been shown to utilise the Wnt/Ca 2+ pathway [11,37]. There is also some evidence that Ryk may activate the Wnt/-catenin pathway by forming a co-receptor complex with Fz8 [36] and that Ryk inhibits Wnt/-catenin signalling via interaction with the E3 ubiquitin ligase Mindbomb1 in response to Wnt3a [38]. Currently, our knowledge of the Ryk signalling pathway comes largely from analysis of its axon guidance function.…”

Section: Ryk a Novel Wnt Receptormentioning

confidence: 99%

The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration

Clark

Liu

Cooper

2014

Sci. China Life Sci.

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In the developing embryo, nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous system. Molecular navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth cone. Axon-bound receptors detect these gradients and determine the trajectory of the migrating growth cone. In contrast to their benevolent role in the developing nervous system, repulsive guidance receptors are detrimental to the axon's ability to regenerate after injury in the adult. In this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor, Ryk/Derailed in axon navigation in the embryonic nervous system (the Yin function). Specifically, we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system, the corticospinal tract and the corpus callosum. Recent studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord injury. Thus, we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth (the Yang function).Ryk, Derailed, Wnt, Wnt signalling, axon guidance, axonal regeneration, spinal cord injury Citation:Clark CEJ, Liu YB, Cooper HM. The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration.

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Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/β-catenin signaling

Abstract: MIB1 ubiquitin ligase–mediated regulation of internalization of the Wnt receptor RYK is necessary for response to Wnt3a ligand in cell culture and C. elegans.

Cited by 92 publications

References 47 publications

Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth

Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth

The E3 ubiquitin ligase Mib1 regulates Plk4 and centriole biogenesis

The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration

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