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Septate-Junction-Dependent Luminal Deposition  of Chitin Deacetylases Restricts  Tube Elongation in the Drosophila Trachea
Stockholm University, Faculty of Science, The Wenner-Gren Institute . (Christos Samakovlis)
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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2006 (English)In: Current Biology, ISSN 0960-9822, Vol. 16, no 2, 180-185 p.Article in journal (Refereed) Published
Abstract [en]

The function of tubular epithelial organs like the kidney and lung is critically dependent on the length and diameter of their constituting branches. Genetic analysis of tube size control during Drosophila tracheal development has revealed that epithelial septate junction (SJ) components and the dynamic chitinous luminal matrix coordinate tube growth. However, the underlying molecular mechanisms controlling tube expansion so far remained elusive. Here, we present the analysis of two luminal chitin binding proteins with predicted polysaccharide deacetylase activities (ChLDs). ChLDs are required to assemble the cable-like extracellular matrix (ECM) and restrict tracheal tube elongation. Overexpression of native, but not of mutated, ChLD versions also interferes with the structural integrity of the intraluminal ECM and causes aberrant tube elongation. Whereas ChLD mutants have normal SJ structure and function, the luminal deposition of the ChLD requires intact cellular SJs. This identifies a new molecular function for SJs in the apical secretion of ChLD and positions ChLD downstream of the SJs in tube length control. The deposition of the chitin luminal matrix first promotes and coordinates radial tube expansion. We propose that the subsequent structural modification of chitin by chitin binding deacetylases selectively instructs the termination of tube elongation to the underlying epithelium.

Place, publisher, year, edition, pages
2006. Vol. 16, no 2, 180-185 p.
Research subject
Developmental Biology
Identifiers
URN: urn:nbn:se:su:diva-32565DOI: 10.1016/j.cub.2005.11.074OAI: oai:DiVA.org:su-32565DiVA: diva2:280971
Available from: 2009-12-14 Created: 2009-12-14 Last updated: 2010-04-20Bibliographically approved
In thesis
1. New roles for apical secretion and extracellular matrix assembly in Drosophila epithelial morphogenesis
Open this publication in new window or tab >>New roles for apical secretion and extracellular matrix assembly in Drosophila epithelial morphogenesis
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Branched tubular organs, such as the lung and vascular system fulfill the respiratory needs of most animals. Optimal tissue function relies on the uniform sizes and shapes of the constituting branches in each organ. The Drosophila tracheal airways provide a recognized genetic model system for identification and characterization of tube size regulators. We found that the programmed secretion and assembly of the apical extracellular matrix (ECM) is required for the expansion of the trachea and salivary glands (SG) tubes. We have characterized Vermiform (Verm) and Serpentine (Serp), two chitin-binding proteins with predicted polysaccharide deacetylase domains (ChLDs). Verm and Serp mutants show overelongated tubes, suggesting that luminal ECM modification restricts tracheal tube elongation. The luminal deposition of ChLDs, but not other secreted components, depends on paracellular septate junction integrity (SJs) in the tracheal epithelium. Deletion of the deacetylase domain renders Serp-GFP intracellular, arguing that the deacetylase domain harbors uncharacterized secretion signals. To explore this possibility we transferred the deacetylase domain from Serp to Gasp, another tracheal luminal protein, which requires the Emp24 adaptor for ER exit. The Gasp-Deac-GFP chimera was normally secreted in emp24 mutants indicating that the deacetylase domain contains potential ER-exit signals. To identify such signals we characterized conserved sequence motifs in the Serp deacetylase domain. Mutations of the N-glycosylation sites gradually reduced Serp-GFP luminal deposition suggesting that increased glycosylation enhances apical Serp secretion. By contrast, substitutions in three conserved amino acid stretches completely blocked the ER-exit of Serp-GFP. The mutated proteins were N-glycosylated suggesting that the motifs may be involved in a subsequent protein-folding step or facilitate ER exit through interactions with unidentified specific adaptors.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. 64 p.
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-32564 (URN)978-91-7155-952-4 (ISBN)
Public defence
2010-01-29, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript. Available from: 2010-01-07 Created: 2009-12-14 Last updated: 2011-02-28Bibliographically approved
2. Grainy head target genes in epithelial morphogenesis and wound healing
Open this publication in new window or tab >>Grainy head target genes in epithelial morphogenesis and wound healing
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

grainy head (grh) genes encode a family of transcription factors conserved from fly to human. Drosophila grh is the founding member of this gene family and has multiple functions, including tracheal tube size control, epidermal barrier formation and reconstruction after wounding. To understand the underlying molecular mechanism of grh functions, we tried to isolate its direct targets and analyze their function. We identified ten grh targets by combining bioinformatics and genetics. Grh directly controls the expression of stitcher (stit), which encodes a Ret family receptor tyrosine kinase (RTK), during both development and wound healing. Stit promotes actin cable assembly and induces extracellular signal-regulated kinase (ERK) phosphorylation around the wound edges upon injury. Stit also activates barrier repair genes and its own expression at the wound sites in a Grh-dependent manner. This positive feedback loop ensures efficient epidermal wound repair. In addition, Grh regulates the expression of multiple genes involved in chitin biosynthesis or modification. Most of the genes are required for tracheal tube size control. Two of them, verm and serp, encode related putative luminal chitin deacetylases. The functional analysis of verm and serp identifies an important role of luminal chitin matrix modification in limiting tracheal tube elongation. Therefore, it is very likely that Grh controls tracheal tube size through regulating multiple targets involved in the assembly or modification of luminal chitin matrix. Grh also directly activates the epidermal expression of Peptidoglycan recognition protein LC (PGRP-LC) gene that is required for the induction of antimicrobial peptides (AMPs) upon infection. Furthermore, ectopically expressing Grh is sufficient to induce AMP Cecropin A lacZ reporter (CecA-LacZ) in the embryonic epidermis. These results suggest a new function of Grh in the local immune responses in Drosophila barrier epithelia.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. 60 p.
Keyword
grh, targets, epidermal wound repair, tracheal tube size control, local immune responses, stit, verm, serp, PGRP-LC, CecA-LacZ
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-38377 (URN)978-91-7447-004-8 (ISBN)
Public defence
2010-05-21, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following papers was unpublished and had a status as follows: Paper 1: Manuscript. Available from: 2010-04-28 Created: 2010-04-12 Last updated: 2010-04-27Bibliographically approved

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