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Apical targeting of the formin Diaphanous in Drosophila tubular epithelia
- Source :
- eLife, vol 2, iss 2, eLife, Vol 2 (2013), Rousso, T; Shewan, AM; Mostov, KE; Schejter, ED; & Shilo, BZ. (2013). Apical targeting of the formin diaphanous in Drosophila tubular epithelia. eLife, 2013(2). doi: 10.7554/eLife.00666. UCSF: Retrieved from: http://www.escholarship.org/uc/item/0pb3d50d, eLife
- Publication Year :
- 2013
- Publisher :
- eScholarship, University of California, 2013.
-
Abstract
- Apical secretion from epithelial tubes of the Drosophila embryo is mediated by apical F-actin cables generated by the formin-family protein Diaphanous (Dia). Apical localization and activity of Dia are at the core of restricting F-actin formation to the correct membrane domain. Here we identify the mechanisms that target Dia to the apical surface. PI(4,5)P2 levels at the apical membrane regulate Dia localization in both the MDCK cyst model and in Drosophila tubular epithelia. An N-terminal basic domain of Dia is crucial for apical localization, implying direct binding to PI(4,5)P2. Dia apical targeting also depends on binding to Rho1, which is critical for activation-induced conformational change, as well as physically anchoring Dia to the apical membrane. We demonstrate that binding to Rho1 facilitates interaction with PI(4,5)P2 at the plane of the membrane. Together these cues ensure efficient and distinct restriction of Dia to the apical membrane. DOI: http://dx.doi.org/10.7554/eLife.00666.001<br />eLife digest Many physiological processes are directional, which means that tissues and organs often need a sense of spatial orientation in order to function properly. In most tissues, this sense of direction relies on certain proteins and infrastructure components of the cell being located in specific subcellular regions, rather than being distributed in a more symmetrical fashion throughout the cell: the latter phenomenon is known as cell polarity. Exocrine tissues (that is, glands) are composed of tubular epithelial cells organized around a central lumen: the cells in the gland secrete various products (such as enzymes) into the lumen, so that they can be carried to the target organ elsewhere in the body. Epithelial cells in these tissues are therefore polarized to enable directional transport to the lumen. An example of cell polarity is a network of actin filaments that lines the apical surface of these cells (the surface nearest the common lumen). This actin network helps to shuttle cargo to the lumen by assisting with directional, coordinated secretion, among other processes. In fruitflies, the construction of the apical actin network depends on the presence of a protein called Diaphanous. However, the signals that lead to the localization of this protein near the apical membrane of the cells are not well understood. Now Rousso et al. report that a modified lipid, called PI(4,5)P2, is involved in this localization. However, they also show that this lipid does not govern the apical localization of Diaphanous on its own: rather, an enzyme called Rho1 must also be present to assist with the localization of Diaphanous and to ensure that actin is deposited in the correct place. Rousso et al. also demonstrate that PI(4,5)P2-mediated localization of Drosophila Diaphanous occurs in mammalian cells. Lipid-protein collaboration also targets other proteins to the apical membrane. A common mechanism may therefore underlie cell polarity in tubular organ tissues in flies and mammals. DOI: http://dx.doi.org/10.7554/eLife.00666.002
- Subjects :
- Phosphatidylinositol 4,5-Diphosphate
Conformational change
Protein Conformation
tubular epithelia
Sequence Homology
Madin Darby Canine Kidney Cells
PI(4,5)P2
Protein structure
Drosophila Proteins
apical localization
Biology (General)
0303 health sciences
biology
D. melanogaster
General Neuroscience
030302 biochemistry & molecular biology
General Medicine
Cell biology
Phosphatidylinositol 4
Amino Acid
Drosophila melanogaster
Formins
5-Diphosphate
Medicine
PI(4
Drosophila Protein
Research Article
QH301-705.5
Science
formin
1.1 Normal biological development and functioning
Green Fluorescent Proteins
Molecular Sequence Data
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Dogs
Underpinning research
5)P2
Animals
Secretion
Amino Acid Sequence
030304 developmental biology
General Immunology and Microbiology
Sequence Homology, Amino Acid
Diaphanous
Apical constriction
Cell Biology
Apical membrane
biology.organism_classification
Developmental Biology and Stem Cells
biology.protein
Rho1
Generic health relevance
Biochemistry and Cell Biology
Carrier Proteins
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- eLife, vol 2, iss 2, eLife, Vol 2 (2013), Rousso, T; Shewan, AM; Mostov, KE; Schejter, ED; & Shilo, BZ. (2013). Apical targeting of the formin diaphanous in Drosophila tubular epithelia. eLife, 2013(2). doi: 10.7554/eLife.00666. UCSF: Retrieved from: http://www.escholarship.org/uc/item/0pb3d50d, eLife
- Accession number :
- edsair.doi.dedup.....46b99e796bc6a9b288ec576567cf2c0f