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: 3.84). 04/2007; 34(3):481-92. DOI: 10.1016/j.mcn.2006.12.002
Source: PubMed


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.

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Available from: Sonya E Craig, Apr 02, 2015
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    • "These interactions and the biochemical events that follow, result in changes to tumor cell surface receptors and remodeling of the ECM by proteolysis [Furnari et al., 2007; Nakada et al., 2007; Rao, 2003; Sala et al., 2008; Teodorczyk and Martin-Villalba, 2010]. Gliomas overexpress growth factor receptor tyrosine kinases (RTKs) and their ligands, creating a situation for autocrine Studies from our laboratory demonstrated that catalytic activity of PTPμ is essential for regulating PTPμ-mediated processes [Burden-Gulley and Brady-Kalnay, 1999; Ensslen- Craig and Brady-Kalnay, 2005; Oblander et al., 2007]. To gain a better understanding of PTPμ function, a number of direct PTPμ binding proteins and potential substrates have been identified including, RACK1, p120, IQGAP1 and BCCIP [Mourton et al., 2001; Phillips- Mason et al., 2006; Phillips-Mason et al., 2008; Zondag et al., 2000]. "
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    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 · 3.26 Impact Factor
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    • "Infection of retinal cells with antisense PTPμ-HSV reduced the overall PTPμ protein levels by 60% (Fig. 7A). This reduction in protein is similar to what we have previously published with the antisense PTPμ-HSV construct [Ensslen et al., 2003;Ensslen-Craig and Brady-Kalnay, 2005;Oblander et al., 2007]. Antisense BCCIP-HSV had little to no effect on PTPμ protein expression. "
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    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 · 3.26 Impact Factor
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    • "Notch and basic helix-loop helix protein (bHLH) play a role in neural determination and differentiation of RGC [2,3]. Another protein, Brn3 was found to be important for terminal differentiation of RGC precursors [4] Neurite outgrowth in RGCs can be promoted by E-cadherin [5], and RGCs axons are navigated by Ephrin and Ephrin receptors [6,7]. On the other hand, PaxL had an inhibitory effect on ganglion cell development [8]. "
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    Proteome Science 02/2008; 6(1):3. DOI:10.1186/1477-5956-6-3 · 1.73 Impact Factor
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