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      Control of cortical microtubule organization and desmosome stability by centrosomal proteins

      other
      1 , 1 , 2 , *
      Bioarchitecture
      Landes Bioscience
      Lis1, desmoplakin, desmosome, epidermis, microtubule

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          Abstract

          In many tissues microtubules reorganize into non-centrosomal arrays in differentiated cells. In the epidermis, proliferative basal cells have a radial array of microtubules organized around a centrosome, while differentiated cells have cortical microtubules. The desmosomal protein desmoplakin is required for the microtubules to organize around the cell cortex. Furthermore, the centrosomal and/or microtubule-associated proteins ninein, Lis1, Ndel1, and CLIP170 are recruited to the cell cortex, where they have been implicated in the cortical organization of microtubules. Recently, it has been shown that in Lis1-null epidermis, microtubules are disorganized in the differentiated layers of the epidermis. Furthermore, Lis1-null mice die perinatally due to dehydration. This is due, in part, to the unexpected desmosome phenotype observed in Lis1-null skin. Upon loss of Lis1, desmosomal proteins become less stable. Here, we propose that Lis1 may regulate desmosomal stability through its binding partners Nde1/Ndel1 and dynein.

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          Most cited references22

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          A core function for p120-catenin in cadherin turnover

          p120-catenin stabilizes epithelial cadherin (E-cadherin) in SW48 cells, but the mechanism has not been established. Here, we show that p120 acts at the cell surface to control cadherin turnover, thereby regulating cadherin levels. p120 knockdown by siRNA expression resulted in dose-dependent elimination of epithelial, placental, neuronal, and vascular endothelial cadherins, and complete loss of cell–cell adhesion. ARVCF and δ-catenin were functionally redundant, suggesting that proper cadherin-dependent adhesion requires the presence of at least one p120 family member. The data reveal a core function of p120 in cadherin complexes, and strongly predict a dose-dependent loss of E-cadherin in tumors that partially or completely down-regulate p120.
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            LIS1 and NudE induce a persistent dynein force-producing state.

            Cytoplasmic dynein is responsible for many aspects of cellular and subcellular movement. LIS1, NudE, and NudEL are dynein interactors initially implicated in brain developmental disease but now known to be required in cell migration, nuclear, centrosomal, and microtubule transport, mitosis, and growth cone motility. Identification of a specific role for these proteins in cytoplasmic dynein motor regulation has remained elusive. We find that NudE stably recruits LIS1 to the dynein holoenzyme molecule, where LIS1 interacts with the motor domain during the prepowerstroke state of the dynein crossbridge cycle. NudE abrogates dynein force production, whereas LIS1 alone or with NudE induces a persistent-force dynein state that improves ensemble function of multiple dyneins for transport under high-load conditions. These results likely explain the requirement for LIS1 and NudE in the transport of nuclei, centrosomes, chromosomes, and the microtubule cytoskeleton as well as the particular sensitivity of migrating neurons to reduced LIS1 expression. Copyright 2010 Elsevier Inc. All rights reserved.
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              A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system.

              Mutations in mammalian Lis1 (Pafah1b1) result in neuronal migration defects. Several lines of evidence suggest that LIS1 participates in pathways regulating microtubule function, but the molecular mechanisms are unknown. Here, we demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL, a murine homolog of the Aspergillus nidulans nuclear migration mutant NudE. LIS1 and NUDEL colocalize predominantly at the centrosome in early neuroblasts but redistribute to axons in association with retrograde dynein motor proteins. NUDEL is phosphorylated by Cdk5/p35, a complex essential for neuronal migration. NUDEL and LIS1 regulate the distribution of CDHC along microtubules, and establish a direct functional link between LIS1, NUDEL, and microtubule motors. These results suggest that LIS1 and NUDEL regulate CDHC activity during neuronal migration and axonal retrograde transport in a Cdk5/p35-dependent fashion.
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                Author and article information

                Journal
                Bioarchitecture
                Bioarchitecture
                BIOA
                Bioarchitecture
                Landes Bioscience
                1949-0992
                1949-100X
                01 September 2011
                01 September 2011
                : 1
                : 5
                : 221-224
                Affiliations
                [1 ]Department of Cell Biology; Duke University Medical Center; Durham, NC USA
                [2 ]Department of Dermatology; Duke University Medical Center; Durham, NC USA
                Author notes
                [* ]Correspondence to: Terry Lechler; Email: terry.lechler@ 123456duke.edu
                Article
                2011BIOARCHITECTURE0044 18403
                10.4161/bioa.18403
                3384573
                22754612
                2567950f-081a-422b-8b44-5cce135d6af7
                Copyright © 2011 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

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                Categories
                Perspective

                Molecular biology
                lis1,epidermis,desmosome,desmoplakin,microtubule
                Molecular biology
                lis1, epidermis, desmosome, desmoplakin, microtubule

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