Cell-type-specific expression of protein tyrosine kinase-related receptor RYK in the central nervous system of the rat

Kamitori, Kazuyo; Machide, Mitsuru; Tomita, Kazuhiko; Nakafuku, Masato; Kohsaka, Shinichi

doi:10.1016/s0169-328x(02)00358-3

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…Although Ryk expression has been previously described in the developing spinal cord, 33,46,47 its expression in the unlesioned adult spinal cord was unclear. In this way, Ryk mRNA expression was detected in the adult spinal cord by in situ hybridization (ISH), 48 in agreement with our results that showed Ryk mRNA expression using RT-qPCR.…”

Section: Discussionmentioning

confidence: 98%

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

González

Fernández-Martos

Arenas

et al. 2013

Journal of Neurotrauma

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Wnt proteins play a critical role in central nervous system development and have been implicated in several neuropathologies, including spinal cord injury (SCI). Ryk, an unconventional Wnt receptor, regulates axonal regeneration after SCI, although its expression pattern in this neuropathology remains unclear. Therefore, we sought to define the spatiotemporal and cellular pattern of Ryk expression after a contusive SCI in adult rats using quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis. Under physiological conditions, Ryk is expressed in neurons, astrocytes, and blood vessels, but not in oligodendrocytes, microglia, NG2+ glial precursor cells, or axonal projections. Following SCI, we observed an increase in Ryk mRNA expression from 24 h post-injury until 7 days post-injury, whereas its protein levels were significantly augmented at 7 and 14 days post-injury. Moreover, the spatial and cellular Ryk expression pattern was altered in the damaged tissue, where this receptor was observed in reactive astrocytes and microglia/macrophages, NG2+ glial precursors, fibronectin + cells, oligodendrocytes, and axons. In conclusion, we demonstrate that Ryk is expressed in the unlesioned spinal cord and that, after SCI, its spatiotemporal and cellular expression pattern changed dramatically, being expressed in cells involved in the spinal cord response to damage.

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Section: Discussionmentioning

confidence: 98%

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

González

Fernández-Martos

Arenas

et al. 2013

Journal of Neurotrauma

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“…However, the blockade of the Wnt‐3‐induced neurogenesis observed upon Fz‐8Fc and Dkk‐1 cotreatment was partial. A possible contribution of Ryk and its intracellular C‐terminal domain to the Wnt‐3‐induced neurogenesis in the spinal cord remains to be investigated (Kamitori et al,2002; Lyu et al,2008).…”

Section: Discussionmentioning

confidence: 99%

Wnt‐3a and Wnt‐3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling

David¹,

Cantı́²,

Herreros³

2010

J of Neuroscience Research

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Wnt factors regulate neural stem cell development and neuronal connectivity. Here we investigated whether Wnt-3a and Wnt-3, expressed in the developing spinal cord, regulate proliferation and the neuronal differentiation of spinal cord neural precursors (SCNP). Wnt-3a promoted a sustained increase of SCNP proliferation and decreased the expression of cyclin-dependent kinase inhibitors. In contrast, Wnt-3 transiently enhanced SCNP proliferation and increased neurogenesis through β-catenin signaling. Furthermore, both Wnt-3a and Wnt-3 stimulated neurite outgrowth in SCNP-derived neurons through β-catenin- and TCF4-dependent transcription. Glycogen synthase kinase-3β inhibitors mimicked Wnt signaling and promoted neurite outgrowth in established cultures. We conclude that Wnt-3a and Wnt-3 factors signal through the canonical Wnt/β-catenin pathway to regulate different aspects of SCNP development. These findings may be of therapeutic interest for the treatment of neurodegenerative diseases and nerve injury.

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“…Lipofectamine 2000 (Invitrogen) was used for transfection according to the manufacturer's protocols. MNS-70 is the cell line established from rat neural stem cell ( 53 ).…”

Section: Methodsmentioning

confidence: 99%

Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain

Hatayama¹,

Tomizawa²,

Sakai‐Kato³

et al. 2008

Human Molecular Genetics

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Disruptions in ZIC3 cause heterotaxy, a congenital anomaly of the left–right axis. ZIC3 encodes a nuclear protein with a zinc finger (ZF) domain that contains five tandem C2H2 ZF motifs. Missense mutations in the first ZF motif (ZF1) result in defective nuclear localization, which may underlie the pathogenesis of heterotaxy. Here we revealed the structural and functional basis of the nuclear localization signal (NLS) of ZIC3 and investigated its relationship to the defect caused by ZF1 mutation. The ZIC3 NLS was located in the ZF2 and ZF3 regions, rather than ZF1. Several basic residues interspersed throughout these regions were responsible for the nuclear localization, but R320, K337 and R350 were particularly important. NMR structure analysis revealed that ZF1–4 had a similar structure to GLI ZF, and the basic side chains of the NLS clustered together in two regions on the protein surface, similar to classical bipartite NLSs. Among the residues for the ZF1 mutations, C253 and H286 were positioned for the metal chelation, whereas W255 was positioned in the hydrophobic core formed by ZF1 and ZF2. Tryptophan 255 was a highly conserved inter-finger connector and formed part of a structural motif (tandem CXW-C-H-H) that is shared with GLI, Glis and some fungal ZF proteins. Furthermore, we found that knockdown of Karyopherin α1/α6 impaired ZIC3 nuclear localization, and physical interactions between the NLS and the nuclear import adapter proteins were disturbed by mutations in the NLS but not by W255G. These results indicate that ZIC3 is imported into the cell nucleus by the Karyopherin (Importin) system and that the impaired nuclear localization by the ZF1 mutation is not due to a direct influence on the NLS.

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Cell-type-specific expression of protein tyrosine kinase-related receptor RYK in the central nervous system of the rat

Cited by 7 publications

References 38 publications

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

Wnt‐3a and Wnt‐3 differently stimulate proliferation and neurogenesis of spinal neural precursors and promote neurite outgrowth by canonical signaling

Functional and structural basis of the nuclear localization signal in the ZIC3 zinc finger domain

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