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RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone.

ABSTRACT: Many of the mitoses that produce pyramidal neurons in neocortex occur at the dorsolateral surface of the lateral ventricles in the embryo. RanBPM was found in a yeast two-hybrid screen to potentially interact with citron kinase (CITK), a protein shown previously to localize to the surface of the lateral ventricles and to be essential to neurogenic mitoses. Similar to its localization in epithelia, RanBPM protein is concentrated at the adherens junctions in developing neocortex. The biochemical interaction between CITK and RanBPM was confirmed in coimmunoprecipitation and protein overlay experiments. To test for a functional role of RanPBM in vivo, we used in utero RNAi. RanBPM RNAi decreased the polarization of CITK to the ventricular surface, increased the number of cells in mitosis, and decreased the number of cells in cytokinesis. Finally, the effect of RanBPM knockdown on mitosis was reversed in embryos mutant for CITK. Together, these results indicate that RanBPM, potentially through interaction with CITK, plays a role in the progression of neocortical precursors through M-phase at the ventricular surface.

SUBMITTER: Chang Y

PROVIDER: S-EPMC2933829 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone.

Chang Yoonjeung Y Paramasivam Murugan M Girgenti Matthew J MJ Walikonis Randall S RS Bianchi Elisabetta E LoTurco Joseph J JJ

Developmental neurobiology 20100101 1

Many of the mitoses that produce pyramidal neurons in neocortex occur at the dorsolateral surface of the lateral ventricles in the embryo. RanBPM was found in a yeast two-hybrid screen to potentially interact with citron kinase (CITK), a protein shown previously to localize to the surface of the lateral ventricles and to be essential to neurogenic mitoses. Similar to its localization in epithelia, RanBPM protein is concentrated at the adherens junctions in developing neocortex. The biochemical i ...[more]

PMID: 19790105

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Project description:RanBPM is a ubiquitous protein that has been reported to regulate several cellular processes through interactions with various proteins. However, it is not known whether RanBPM may regulate gene expression patterns. As it has been shown that RanBPM interacts with a number of transcription factors, we hypothesized that it may have wide ranging effects on gene expression that may explain its function. To test this hypothesis, we generated stable RanBPM shRNA cell lines to analyze the effect of RanBPM on global gene expression. Microarray analyses were conducted comparing the gene expression profile of Hela and HCT116 RanBPM shRNA cells versus control shRNA cells. We identified 167 annotated genes significantly up- or down-regulated in the two cell lines. Analysis of the gene set revealed that down-regulation of RanBPM led to gene expression changes that affect regulation of cell, tissue, and organ development and morphology, as well as biological processes implicated in tumorigenesis. Analysis of Transcription Factor Binding Sites (TFBS) present in the gene set identified several significantly over-represented transcription factors of the Forkhead, HMG, and Homeodomain families of transcription factors, which have previously been demonstrated as having important roles in development and tumorigenesis. In addition, the combined results of these analyses suggested that several signaling pathways were affected by RanBPM down-regulation, including ERK1/2, Wnt, Notch, and PI3K/Akt pathways. Lastly, analysis of selected target genes by quantitative RT-qPCR confirmed the changes revealed by microarray. Several of the genes up-regulated in RanBPM shRNA cells encode proteins with known oncogenic functions, such as the RON tyrosine kinase, the adhesion molecule L1CAM, and transcription factor ELF3/ESE-1, suggesting that RanBPM functions as a tumor suppressor to prevent deregulated expression of these genes. Altogether, these results suggest that RanBPM does indeed function to regulate many genomic events that regulate embryonic, tissue, and cellular development as well as those involved in cancer development and progression.

Dataset Information

RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone.

Publications

RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone.

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