E-cadherin promotes retinal ganglion cell neurite outgrowth in a protein tyrosine phosphatase-mu-dependent manner.

Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4960, USA.
Molecular and Cellular Neuroscience (Impact Factor: 3.73). 04/2007; 34(3):481-92. DOI: 10.1016/j.mcn.2006.12.002
Source: PubMed

ABSTRACT During development of the visual system, retinal ganglion cells (RGCs) require cell-cell adhesion molecules and extracellular matrix proteins for axon growth. In this study, we demonstrate that the classical cadherin, E-cadherin, is expressed in RGCs from E6 to E12 and promotes neurite outgrowth from all regions of the chick retina at E6, E8 and E10. E-cadherin is also expressed in the optic tectum. E-cadherin adhesion blocking antibodies specifically inhibit neurite outgrowth on an E-cadherin substrate. The receptor-type protein tyrosine phosphatase, PTPmu, associates with E-cadherin. In this manuscript, we demonstrate that antisense-mediated down-regulation of PTPmu, overexpression of catalytically inactive PTPmu and perturbation of endogenous PTPmu using a specific PTPmu inhibitor peptide results in a substantial reduction in neurite outgrowth on E-cadherin. Taken together, these findings demonstrate that E-cadherin is an important adhesion molecule for chick RGC neurite outgrowth and suggest that PTPmu expression and catalytic activity are required for outgrowth on an E-cadherin substrate.

Download full-text


Available from: Sonya E Craig, Apr 02, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The receptor protein tyrosine phosphatase PTPµ has a cell-adhesion molecule-like extracellular segment and a catalytically active intracellular segment. This structure gives PTPµ the ability to transduce signals in response to cell-cell adhesion. Full-length PTPµ is down-regulated in glioma cells by proteolysis which is linked to increased migration of these cells in the brain. To gain insight into the substrates PTPµ may be dephosphorylating to suppress glioma cell migration, we used a substrate trapping method to identify PTPµ substrates in tumor cell lines. We identified both PKCδ and PLCγ1 as PTPµ substrates. As PLCγ1 activation is linked to increased invasion of cancer cells, we set out to determine whether PTPµ may be upstream of PLCγ1 in regulating glioma cell migration. We conducted brain slice assays using U87-MG human glioma cells in which PTPµ expression was reduced by shRNA to induce migration. Treatment of the same cells with PTPµ shRNA and a PLCγ1 inhibitor prevented migration of the cells within the brain slice. These data suggest that PLCγ1 is downstream of PTPµ and that dephosphorylation of PLCγ1 is likely to be a major pathway through which PTPµ suppresses glioma cell migration.
    Journal of Cellular Biochemistry 01/2011; 112(1):39-48. DOI:10.1002/jcb.22710 · 3.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The receptor protein tyrosine phosphatase PTPmu belongs to a family of adhesion molecules that contain cell-cell adhesion motifs in their extracellular segments and catalytic domains within their intracellular segments. The ability of PTPmu both to mediate adhesion and exhibit enzymatic activity makes PTPmu an excellent candidate to transduce signals in response to cell-cell adhesion. In an effort to identify downstream signaling partners of PTPmu, we performed a modified yeast two-hybrid screen using the first tyrosine phosphatase domain of PTPmu as bait. We isolated an interacting clone encoding BRCA2 and CDKN1A interacting protein (BCCIP) from a HeLa cell library. BCCIP is a p21 and BRCA2 interacting protein that has been shown to play roles in both cell cycle arrest and DNA repair. In this manuscript, we confirm the interaction between BCCIP and PTPmu identified in yeast using in vitro biochemical studies and characterize BCCIP as a PTPmu binding protein. We demonstrate that BCCIP is phosphorylated by the Src tyrosine kinase and dephosphorylated by the PTPmu tyrosine phosphatase in vitro. Furthermore, we show that BCCIP is required for both the permissive and repulsive functions of PTPmu in neurite outgrowth assays, suggesting BCCIP and PTPmu are in a common signal transduction pathway.
    Journal of Cellular Biochemistry 11/2008; 105(4):1059-72. DOI:10.1002/jcb.21907 · 3.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is no report on the gene expression profile of retinoblastoma (Rb). We analyzed the gene expression profile of Rb by the microarray technique. One thousand four genes were upregulated and 481 genes were downregulated. Microarray data were confirmed by semiquantitative RT-PCR for 5 genes in Rb samples: CDC25A, C17orf75, ERBB3, LATS2, and CHFR. Clusters of differentially expressed genes were identified on chromosomes 1, 16, and 17. Based on the expression profile, we hypothesized that the PI3K/AKT/mTOR (insulin signaling) pathway might be dysregulated in Rb. Our semiquantitative RT-PCR analysis of the PIK3CA, AKT1, FRAP1, and RPS6KB1 genes in Rb samples supported this hypothesis. We suggest that known inhibitors of this pathway could be evaluated for the treatment of Rb.
    Genomics 10/2007; 90(3):344-53. DOI:10.1016/j.ygeno.2007.05.002 · 2.79 Impact Factor