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COPI Vesicle Transport Is a Common Requirement for Tube Expansion in Drosophila
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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2008 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 09 AprArticle in journal (Refereed) Published
Abstract [en]

Background Tube expansion defects like stenoses and atresias cause devastating human diseases. Luminal expansion during organogenesis begins to be elucidated in several systems but we still lack a mechanistic view of the process in many organs. The Drosophila tracheal respiratory system provides an amenable model to study tube size regulation. In the trachea, COPII anterograde transport of luminal proteins is required for extracellular matrix assembly and the concurrent tube expansion.

Principal Findings We identified and analyzed Drosophila COPI retrograde transport mutants with narrow tracheal tubes. γCOP mutants fail to efficiently secrete luminal components and assemble the luminal chitinous matrix during tracheal tube expansion. Likewise, tube extension is defective in salivary glands, where it also coincides with a failure in the luminal deposition and assembly of a distinct, transient intraluminal matrix. Drosophila γCOP colocalizes with cis-Golgi markers and in γCOP mutant embryos the ER and Golgi structures are severely disrupted. Analysis of γCOP and Sar1 double mutants suggests that bidirectional ER-Golgi traffic maintains the ER and Golgi compartments and is required for secretion and assembly of luminal matrixes during tube expansion.

Conclusions/Significance Our results demonstrate the function of COPI components in organ morphogenesis and highlight the common role of apical secretion and assembly of transient organotypic matrices in tube expansion. Intraluminal matrices have been detected in the notochord of ascidians and zebrafish COPI mutants show defects in notochord expansion. Thus, the programmed deposition and growth of distinct luminal molds may provide distending forces during tube expansion in diverse organs.

Place, publisher, year, edition, pages
2008. Vol. 09 Apr
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
URN: urn:nbn:se:su:diva-32569DOI: 10.1371/journal.pone.0001964ISI: 000260795500033OAI: oai:DiVA.org:su-32569DiVA: diva2:280973
Available from: 2009-12-15 Created: 2009-12-14 Last updated: 2017-12-12Bibliographically 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. Airway maturation in Drosophila
Open this publication in new window or tab >>Airway maturation in Drosophila
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Tubes are a fundamental unit of organ design. Most of our major organs like the lung, kidney and vasculature are composed primarily of tubes. To identify fundamental biological principles of tubular organ formation we used the respiratory organ of Drosophila melanogaster, the trachea.This work dissects embryonic trachea maturation. Three precise epithelial transitions occur during airway maturation. A secretion burst deposits proteins into the lumen; then luminal material is cleared and finally liquid is removed. We identified the cellular mechanisms behind these transitions. Sar1 and γCOP are required for protein secretion, matrix assembly and tube expansion. Rab5-dependent endocytic activity internalizes and clears luminal contents. The data show how programmed transitions in cellular activities form functional airways, and may reflect a general mechanism in respiratory organ morphogenesis.We further focused on tube size regulation. We identified Melanotransferrin, a new component of septate junctions that limits tracheal tube elongation. MTf is a lipid- modified, iron-binding protein attached to epithelial cell membranes, similarly to its human homologue. We show that septate junction assembly during epithelial maturation relies on endocytosis and apicolateral recycling of iron-bound MTf. Mouse MTf complements the defects of Drosophila MTf mutants. This provides the first genetic model for the functional dissection of MTf in epithelial morphogenesis. In the last part, we describe two genes, which are selectively involved in tube diameter expansion. Obst-A and Gasp are closely related proteins with characteristic chitin-binding domains. They are strongly expressed in the trachea at the time of lumen expansion. The single and double mutants cause a tube diameter reduction, whereas their overexpression leads to its increase. We propose that Obst-A and Gasp organize luminal matrix assembly and thereby regulate the extent of tube diameter expansion.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2011. 18 p.
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-62419 (URN)978-91-7447-338-4. (ISBN)
Public defence
2011-10-21, Högbomsalen, Geovetenskapens hus, Svante Arrhenius väg 12, 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: 2011-09-29 Created: 2011-09-19 Last updated: 2011-09-29Bibliographically approved

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