Homodimerization of the Wnt Receptor DERAILED Recruits the Src Family Kinase SRC64B

Petrova, Iveta; Lahaye, Liza L.; Martiáñez, Tània; Jong, Anja W. M. de; Malessy, Martijn J. A.; Verhaagen, Joost; Noordermeer, Jasprina N.; Fradkin, Lee G.

doi:10.1128/mcb.00169-13

Cited by 14 publications

(15 citation statements)

References 66 publications

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“…The Src non-receptor tyrosine kinases are also required for Wnt5-Derailed-mediated axon guidance. Loss of either Src64B or Src42A leads to disorganised commissures and longitudinal tract defects, a phenotype comparable to that seen in the Wnt5 and Derailed mutants [30,40]. Together these studies suggest that Derailed signals via a novel Src kinase-dependent, non-canonical Wnt pathway, at least in the context of chemorepulsive guidance.…”

Section: Lessons From the Drosophila Nervous Systemmentioning

confidence: 64%

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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Section: Lessons From the Drosophila Nervous Systemmentioning

confidence: 64%

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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“…Drl is a member of the “related to tyrosine kinases” (RYK) family of receptors, and signals axon repulsion independently of its atypical tyrosine kinase domain [147]. Instead, the Wnt5-Drl signaling pathway involves the non-receptor tyrosine kinases Src42A and Src64B through a mechanism that includes Wnt5-induced homodimerization of Drl [148,149]. In a recent study, Long et al [150] used a series of chimeric receptors to demonstrate that the cytoplasmic domains of three known repulsive axon guidance receptors in Drosophila (Robo1, Drl, and Unc5) can act equivalently to repel axons in three distinct axon guidance contexts (midline crossing, commissure choice, and CNS exit).…”

Section: Choice Of Commissurementioning

confidence: 99%

Midline axon guidance in the Drosophila embryonic central nervous system

Howard

Brown

Wadsworth

et al. 2019

Seminars in Cell & Developmental Biology

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Studies in the fruit fly Drosophila melanogaster have provided many fundamental insights into the genetic regulation of neural development, including the identification and characterization of evolutionarily conserved axon guidance pathways and their roles in important guidance decisions. Due to its highly organized and fast-developing embryonic nervous system, relatively small number of neurons, and molecular and genetic tools for identifying, labeling, and manipulating individual neurons or small neuronal subsets, studies of axon guidance in the Drosophila embryonic CNS have allowed researchers to dissect these genetic mechanisms with a high degree of precision. In this review, we discuss the major axon guidance pathways that regulate midline crossing of axons and the formation and guidance of longitudinal axon tracts, two processes that contribute to the development of the precise three-dimensional structure of the insect nerve cord. We focus particularly on recent insights into the roles and regulation of canonical midline axon guidance pathways, and on additional factors and pathways that have recently been shown to contribute to axon guidance decisions at and near the midline.

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“…Since homodimeric proteins are made of two identical chains carrying the same net charge, it is expected that in most cases the electrostatic forces will oppose binding [20]. However, homodimerization is frequently found to be necessary for the function of many proteins [21,22,23,24]. In some cases, the homodimerization results in a formation of a functionally important homodimeric interface [25,26].…”

Section: Introductionmentioning

confidence: 99%

On the electrostatic properties of homodimeric proteins

Campbell

Petukh

Alexov

et al. 2014

J. Theor. Comput. Chem.

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A large fraction of proteins function as homodimers, but it is not always clear why the dimerization is important for functionality since frequently each monomer possesses a distinctive active site. Recent work (PLoS Computational Biology, 9(2), e1002924) indicates that homodimerization may be important for forming an electrostatic funnel in the spermine synthase homodimer which guides changed substrates toward the active centers. This prompted us to investigate the electrostatic properties of a large set of homodimeric proteins and resulted in an observation that in a vast majority of the cases the dimerization indeed results in specific electrostatic features, although not necessarily in an electrostatic funnel. It is demonstrated that the electrostatic dipole moment of the dimer is predominantly perpendicular to the axis connecting the centers of the mass of the monomers. In addition, the surface points with highest potential are located in the proximity of the interfacial plane of the homodimeric complexes. These findings indicate that frequently homodimerization provides specific electrostatic features needed for the function of proteins.

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Homodimerization of the Wnt Receptor DERAILED Recruits the Src Family Kinase SRC64B

Cited by 14 publications

References 66 publications

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

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

Midline axon guidance in the Drosophila embryonic central nervous system

On the electrostatic properties of homodimeric proteins

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