Abstract
We have recently shown that beta-catenin-facilitated export of cadherins from the endoplasmic reticulum requires PX-RICS, a beta-catenin-interacting GTPase-activating protein for Cdc42. Here we show that PX-RICS interacts with isoforms of 14-3-3 and couples the N-cadherin-beta-catenin complex to the microtubule-based molecular motor dynein-dynactin. Similar to knockdown of PX-RICS, knockdown of either 14-3-3zeta or - resulted in the disappearance of N-cadherin and beta-catenin from the cell-cell boundaries. Furthermore, we found that PX-RICS and 14-3-3zeta/ are present in a large multiprotein complex that contains dynein-dynactin components as well as N-cadherin and beta-catenin. Both RNAi- and dynamitin-mediated inhibition of dynein-dynactin function also led to the absence of N-cadherin and beta-catenin at the cell-cell contact sites. Our results suggest that the PX-RICS-14-3-3zeta/ complex links the N-cadherin-beta-catenin cargo with the dynein-dynactin motor and thereby mediates its endoplasmic reticulum export.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins / genetics
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14-3-3 Proteins / metabolism*
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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COS Cells
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Cadherins / genetics
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Cadherins / metabolism*
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Chlorocebus aethiops
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Dynactin Complex
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Dyneins / genetics
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Dyneins / metabolism*
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Endoplasmic Reticulum / genetics
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Endoplasmic Reticulum / metabolism*
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GTPase-Activating Proteins / genetics
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GTPase-Activating Proteins / metabolism*
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Gene Knockdown Techniques
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HeLa Cells
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Humans
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Microtubules / genetics
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Microtubules / metabolism
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism*
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Protein Transport / physiology
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beta Catenin / genetics
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beta Catenin / metabolism*
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cdc42 GTP-Binding Protein / genetics
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cdc42 GTP-Binding Protein / metabolism
Substances
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14-3-3 Proteins
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ARHGAP32 protein, human
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Antigens, CD
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CDH2 protein, human
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Cadherins
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DCTN2 protein, human
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Dynactin Complex
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GTPase-Activating Proteins
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Microtubule-Associated Proteins
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Multiprotein Complexes
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beta Catenin
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Dyneins
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cdc42 GTP-Binding Protein