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Dynein Regulates Epithelial Polarity and the Apical Localization of stardust A mRNA

Journal Article · · PLoS Genetics
 [1];  [2]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; DOE/OSTI
  2. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
Intense investigation has identified an elaborate protein network controlling epithelial polarity. Although precise subcellular targeting of apical and basolateral determinants is required for epithelial architecture, little is known about how the individual determinant proteins become localized within the cell. Through a genetic screen for epithelial defects in the Drosophila follicle cells, we have found that the cytoplasmic Dynein motor is an essential regulator of apico–basal polarity. Our data suggest that Dynein acts through the cytoplasmic scaffolding protein Stardust (Sdt) to localize the transmembrane protein Crumbs, in part through the apical targeting of specific sdt mRNA isoforms. We have mapped the sdt mRNA localization signal to an alternatively spliced coding exon. Intriguingly, the presence or absence of this exon corresponds to a developmental switch in sdt mRNA localization in which apical transcripts are only found during early stages of epithelial development, while unlocalized transcripts predominate in mature epithelia. This work represents the first demonstration that Dynein is required for epithelial polarity and suggests that mRNA localization may have a functional role in the regulation of apico–basal organization. Moreover, we introduce a unique mechanism in which alternative splicing of a coding exon is used to control mRNA localization during development.
Research Organization:
Univ. of California, Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI ID:
1627268
Journal Information:
PLoS Genetics, Journal Name: PLoS Genetics Journal Issue: 1 Vol. 4; ISSN 1553-7404
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

References (65)

Mass transit: Epithelial morphogenesis in theDrosophila egg chamber journal January 2005
DPATJ plays a role in retinal morphogenesis and protects against light-dependent degeneration of photoreceptor cells in theDrosophila eye journal January 2006
Dynein Anchors Its mRNA Cargo after Apical Transport in the Drosophila Blastoderm Embryo journal July 2005
Implication of a 5′ coding sequence in targeting maternal mRNA to the Drosophila oocyte journal November 1997
Structural elements required for the localization of ASH1 mRNA and of a green fluorescent protein reporter particle in vivo journal March 1999
ASH1 mRNA localization in yeast involves multiple secondary structural elementsand Ash1 protein translation journal March 1999
Involvement of microtubule motors in basolateral and apical transport in kidney cells journal December 1994
Conserved signals and machinery for RNA transport in Drosophila oogenesis and embryogenesis journal December 2001
Drosophila Stardust interacts with Crumbs to control polarity of epithelia but not neuroblasts journal December 2001
Direct interaction of two polarity complexes implicated in epithelial tight junction assembly journal January 2003
Organization of vesicular trafficking in epithelia journal March 2005
Moving messages: the intracellular localization of mRNAs journal May 2005
RNA localization in yeast: moving towards a mechanism journal January 2005
Mechanisms of translational regulation in Drosophila journal April 2005
The Drosophila synaptotagmin-like protein bitesize is required for growth and has mRNA localization sequences within its open reading frame journal October 2003
hINADl/PATJ, a Homolog of Discs Lost, Interacts with Crumbs and Localizes to Tight Junctions in Human Epithelial Cells journal July 2002
Tight Junction Protein Par6 Interacts with an Evolutionarily Conserved Region in the Amino Terminus of PALS1/Stardust journal July 2004
Drosophila cytoplasmic dynein, a microtubule motor that is asymmetrically localized in the oocyte. journal September 1994
Cytoplasmic Dynein Regulation by Subunit Heterogeneity and Its Role in Apical Transport journal June 2001
Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia journal December 2003
Adherens junction-dependent and -independent steps in the establishment of epithelial cell polarity in Drosophila journal October 2004
The positioning and segregation of apical cues during epithelial polarity establishment in Drosophila journal August 2005
Cytoplasmic Dynein Function Is Essential in Drosophila melanogaster journal March 1996
Quantitative Analysis of Gene Function in the Drosophila Embryo journal January 2000
Towards understanding CRUMBS function in retinal dystrophies journal October 2006
Intracellular Trafficking of RNA in Neurons journal October 2006
Composition and Formation of Intercellular Junctions in Epithelial Cells journal December 2002
Epithelial Cell Polarity and Cell Junctions in Drosophila journal December 2001
Moving Molecules: mRNA Trafficking in Mammalian Oligodendrocytes and Neurons journal December 2004
Bazooka is a permissive factor for the invasive behavior of discs large tumor cells in Drosophila ovarian follicular epithelia journal May 2003
Compartmentalisation of Rho regulators directs cell invagination during tissue morphogenesis journal October 2006
Identifying loci required for follicular patterning using directed mosaics journal June 1998
Construction of Transgenic Drosophila by Using the Site-Specific Integrase From Phage  C31 journal April 2004
crumbs and stardust Act in a Genetic Pathway That Controls the Organization of Epithelia in Drosophila melanogaster journal September 1993
Apical localization of pair-rule transcripts requires 3′ sequences and limits protein diffusion in the Drosophila blastoderm embryo journal November 1991
Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of drosophila journal July 1995
The Role of the Dynactin Complex in Intracellular Motility book January 1998
Apical Localization of wingless Transcripts Is Required for Wingless Signaling journal April 2001
Drosophila wingless and Pair-Rule Transcripts Localize Apically by Dynein-Mediated Transport of RNA Particles journal April 2001
Intracellular mRNA localization: motors move messages journal December 2002
Implication of a 5′ coding sequence in targeting maternal mRNA to the Drosophila oocyte journal November 1997
Structural elements required for the localization of ASH1 mRNA and of a green fluorescent protein reporter particle in vivo journal March 1999
ASH1 mRNA localization in yeast involves multiple secondary structural elementsand Ash1 protein translation journal March 1999
Protein trafficking in the exocytic pathway of polarized epithelial cells journal December 2001
Computer modelling in combination with in vitro studies reveals similar binding affinities of Drosophila Crumbs for the PDZ domains of Stardust and DmPar-6 journal August 2006
Drosophila Stardust is a partner of Crumbs in the control of epithelial cell polarity journal December 2001
Bazooka provides an apical cue for Inscuteable localization in Drosophila neuroblasts journal December 1999
Adaptation of core mechanisms to generate cell polarity journal April 2003
Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization journal December 2002
Integrated activity of PDZ protein complexes regulates epithelial polarity journal December 2002
RNA localization in yeast: moving towards a mechanism journal January 2005
Putting RNAs in the right place at the right time: RNA localization in the frog oocyte journal January 2005
Mechanisms of translational regulation in Drosophila journal April 2005
hINADl/PATJ, a Homolog of Discs Lost, Interacts with Crumbs and Localizes to Tight Junctions in Human Epithelial Cells journal July 2002
Tight Junction Protein Par6 Interacts with an Evolutionarily Conserved Region in the Amino Terminus of PALS1/Stardust journal July 2004
Apical, Lateral, and Basal Polarization Cues Contribute to the Development of the Follicular Epithelium during Drosophila Oogenesis journal November 2000
The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost journal April 2002
Microtubule-Dependent Vesicle Transport: Modulation of Channel and Transporter Activity in Liver and Kidney journal October 1998
The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium journal September 2003
3′ non-translated sequences in Drosophila cyclin B transcripts direct posterior pole accumulation late in oogenesis and peri-nuclear association in syncytial embryos journal August 1992
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes journal June 1993
The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila journal June 1997
Reciprocal localization of Nod and kinesin fusion proteins indicates microtubule polarity in the Drosophila oocyte, epithelium, neuron and muscle journal January 1997
Different 3′ untranslated regions target alternatively processed hu-li tai shao (hts) transcripts to distinct cytoplasmic locations during Drosophila oogenesis journal October 1999
Unraveling the Genetic Complexity of Drosophila stardust During Photoreceptor Morphogenesis and Prevention of Light-Induced Degeneration journal August 2007

Cited By (30)

Establishing and maintaining cell polarity with mRNA localization inDrosophila journal January 2016
mRNA Localization: Gene Expression in the Spatial Dimension journal February 2009
Cell Polarity in Eggs and Epithelia: Parallels and Diversity journal May 2010
Transcriptome-wide Regulation of Pre-mRNA Splicing and mRNA Localization by Muscleblind Proteins journal August 2012
Quantitative analysis of epithelial morphogenesis in Drosophila oogenesis: New insights based on morphometric analysis and mechanical modeling journal July 2009
Stepwise polarisation of the Drosophila follicular epithelium journal February 2010
The cytoskeletal motor proteins Dynein and MyoV direct apical transport of Crumbs journal March 2020
Dynein light chain 1 functions in somatic cyst cells regulate spermatogonial divisions in Drosophila journal November 2011
Stardust, the Janus-faced partner of Crumbs journal April 2017
Antagonistic Functions of Two Stardust Isoforms inDrosophilaPhotoreceptor Cells journal November 2010
Apical transport of Crumbs maintains epithelial cell polarity posted_content January 2019
Identification of conserved splicing motifs in mutually exclusive exons of 15 insect species journal January 2012
Tissue-specific function of Patj in regulating the Crumbs complex and epithelial polarity journal December 2012
Correction: Shot and Patronin polarise microtubules to direct membrane traffic and biogenesis of microvilli in epithelia journal July 2017
Drosophila Hephaestus/Polypyrimidine Tract Binding Protein Is Required for Dorso-Ventral Patterning and Regulation of Signalling between the Germline and Soma journal July 2013
The Function of Introns journal January 2012
Systematic imaging reveals features and changing localization of mRNAs in Drosophila development journal April 2015
The many functions of mRNA localization during normal development and disease: from pillar to post: mRNA localization in development and disease journal March 2013
Control of cytoplasmic mRNA localization journal October 2011
A Novel Kinesin 13 Protein Regulating Rice Seed Length journal June 2010
Bidirectional selection for body weight on standing genetic variation in a chicken model posted_content January 2018
New mode of mitochondrial transport and polarized sorting regulation by Dynein, Milton and Miro journal January 2016
Shot and Patronin polarise microtubules to direct membrane traffic and biogenesis of microvilli in epithelia journal January 2016
A new mode of mitochondrial transport and polarized sorting regulated by Dynein, Milton and Miro journal December 2016
Dynamics of cortical domains in early Drosophila development journal April 2018
A Screen for Round Egg Mutants in Drosophila Identifies Tricornered, Furry, and Misshapen as Regulators of Egg Chamber Elongation journal March 2012
Bidirectional Selection for Body Weight on Standing Genetic Variation in a Chicken Model journal April 2019
Refinement of Tools for Targeted Gene Expression in Drosophila journal October 2010
Requirement of the Dynein-Adaptor Spindly for Mitotic and Post-Mitotic Functions in Drosophila journal March 2018
Polarization and Myelination in Myelinating Glia journal December 2012

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