The Garz Sec7 domain guanine nucleotide exchange factor for Arf regulates salivary gland development in Drosophila

Szul, Tomasz; Burgess, Jason; Jeon, Mili; Zinn, Kai; Marqués, Guillermo; Brill, Julie A.; Sztul, Elizabeth

doi:10.4161/cl.1.2.15512

Cited by 23 publications

(22 citation statements)

References 69 publications

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“…This is of particular interest because until now none of the known Garz homologues from higher eukaryotes was studied in an organismic context because of the absence of mutants. Nevertheless, a crucial role of Garz in the secretory pathway was demonstrated by biochemical analyses and studies in yeast and mammalian cell cultures (Chantalat et al, 2003;Claude et al, 1999;Niu et al, 2005;Ramaen et al, 2007;Sáenz et al, 2009;Spang et al, 2001;Szul et al, 2007) and in Drosophila by an RNA interference (RNAi) approach (Szul et al, 2011). Recently, Gupta and colleagues also provided evidence of a role of Garz in the endocytic pathway in flies (Gupta et al, 2009).…”

Section: Ems667mentioning

confidence: 99%

“…A similar approach led to the confirmation of Garz as being essential for the regulation of lipid homeostasis in S2 cells (Beller et al, 2008;Guo et al, 2008). Depletion of GBF1 in mammalian HeLa cells and Garz in Drosophila third instar larvae salivary glands provides further evidence for a crucial role of Garz in protein trafficking and secretion (Szul et al, 2011). Recently, garz was identified as a regulator of the noncanonical but highly conserved GEEC (GPI-AP enriched early endosomal compartments) clathrin-and dynamin-independent endocytic pathway (Gupta et al, 2009).…”

Section: Introductionmentioning

confidence: 96%

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GBF1 (Gartenzwerg)-dependent secretion is required for Drosophila tubulogenesis

Wang

Meyer

Ochoa-Espinosa

et al. 2012

Journal of Cell Science

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SummaryHere we report on the generation and in vivo analysis of a series of loss-of-function mutants for the Drosophila ArfGEF, Gartenzwerg. The Drosophila gene gartenzwerg (garz) encodes the orthologue of mammalian GBF1. garz is expressed ubiquitously in embryos with substantially higher abundance in cells forming diverse tubular structures such as salivary glands, trachea, proventriculus or hindgut. In the absence of functional Garz protein, the integrity of the Golgi complex is impaired. As a result, both vesicle transport of cargo proteins and directed apical membrane delivery are severely disrupted. Dysfunction of the Arf1-COPI machinery caused by a loss of Garz leads to perturbations in establishing a polarized epithelial architecture of tubular organs. Furthermore, insufficient apical transport of proteins and other membrane components causes incomplete luminal diameter expansion and deficiencies in extracellular matrix assembly. The fact that homologues of Garz are present in every annotated metazoan genome indicates that secretion processes mediated by the GBF-type ArfGEFs play a universal role in animal development.

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Section: Ems667mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

GBF1 (Gartenzwerg)-dependent secretion is required for Drosophila tubulogenesis

Wang

Meyer

Ochoa-Espinosa

et al. 2012

Journal of Cell Science

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“…ARF1 bound to GTP is required to effect its GTPase activity and mediate cellular function in the context of salivary gland morphogenesis (13). The inactive form of ARF1 is GDP bound.…”

Section: Arf1 Depletion In the Lymph Gland Affects Cell Proliferationmentioning

confidence: 99%

“…In the salivary gland, Garz depletion disrupts the secretory pathway, inhibiting surface delivery of adhesion molecules such as Drosophila E-cadherin (DE-cadherin) and Flamingo. Deregulated trafficking affects the positioning and elongation of epithelial cells leading to disorganized salivary glands (13). Interestingly, DE-cadherin is expressed in prohemocytes of the primary lymph gland lobe (1) and asrij depletion reduces the expression of DE-cadherin leading to premature differentiation (6).…”

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confidence: 99%

ARF1–GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis

Khadilkar

Rodrigues

Mote

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Ras small GTPases including ARFs act as molecular switches to modulate signaling pathways involved in hematopoiesis. Decreased guanine nucleotide exchange factor activity or increased GTPase-activating protein activation are associated with many leukemias, myelodysplastic syndromes, and myeloproliferative disorders. Drosophila is a good model to address questions related to aberrant hematopoiesis. Using Drosophila genetics and gene expression analysis we show tissue-specific function of the ubiquitously expressed endocytic protein, Drosophila ARF1 by interaction of ARF1–GTP with a blood-cell–expressed endocytic protein Asrij. The ARF1–Asrij axis brings about endosomal regulation of multiple signaling pathways in hematopoiesis.

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“…GBF1 family ARF-GEFs have been characterized in yeast (Gea1/2) (Peyroche et al, 1996;Spang et al, 2001), mammalian cells (GBF1) (Claude et al, 1999;Kawamoto et al, 2002) and plants (GNOM, GNL1) (Richter et al, 2007). Drosophila contains a single GBF1 homolog called gartenzwerg (garz) (Kraut et al, 2001;Szul et al, 2011). However, garz loss-offunction mutations were not available and it was not clear which of the six annotated ARF-GEF homologs in Drosophila are involved in COPI vesicle formation at the Golgi.…”

Section: Introductionmentioning

confidence: 99%

The Drosophila Sec7 domain guanine nucleotide exchange factor protein Gartenzwerg localizes at the cis-Golgi and is essential for epithelial tube expansion

Armbruster¹,

Luschnig²

2012

Development

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Protein trafficking through the secretory pathway plays a key role in epithelial organ development and function. The expansion of tracheal tubes in Drosophila depends on trafficking of coatomer protein complex I (COPI)-coated vesicles between the Golgi complex and the endoplasmic reticulum (ER). However, it is not clear how this pathway is regulated. Here we describe an essential function of the Sec7 domain guanine nucleotide exchange factor (GEF) gartenzwerg (garz) in epithelial tube morphogenesis and protein secretion. garz is essential for the recruitment of COPI components and for normal Golgi organization. A GFP-Garz fusion protein is distributed in the cytoplasm and accumulates at the cis-Golgi. Localization to the Golgi requires the C-terminal part of Garz. Conversely, blocking the GDP-GTP nucleotide exchange reaction leads to constitutive Golgi localization, suggesting that Garz cycles in a GEF-activitydependent manner between cytoplasmic and Golgi-membrane-localized pools. The related human ARF-GEF protein GBF1 can substitute for garz function in Drosophila tracheal cells, indicating that the relevant functions of these proteins are conserved. We show that garz interacts genetically with the ARF1 homolog ARF79F and with the ARF1-GAP homolog Gap69C, thus placing garz in a regulatory circuit that controls COPI trafficking in Drosophila. Interestingly, overexpression of garz causes accumulation of secreted proteins in the ER, suggesting that excessive garz activity leads to increased retrograde trafficking. Thus, garz might regulate epithelial tube morphogenesis and secretion by controlling the rate of trafficking of COPI vesicles. Summary Protein trafficking through the secretory pathway plays a key role in epithelial organ development and function. The expansion of tracheal tubes in Drosophila depends on trafficking of coatomer protein complex I (COPI)-coated vesicles between the Golgi complex and the endoplasmic reticulum (ER). However, it is not clear how this pathway is regulated. Here we describe an essential function of the Sec7 domain guanine nucleotide exchange factor (GEF) gartenzwerg (garz) in epithelial tube morphogenesis and protein secretion. garz is essential for the recruitment of COPI components and for normal Golgi organization. A GFP-Garz fusion protein is distributed in the cytoplasm and accumulates at the cis-Golgi. Localization to the Golgi requires the C-terminal part of Garz. Conversely, blocking the GDP-GTP nucleotide exchange reaction leads to constitutive Golgi localization, suggesting that Garz cycles in a GEF-activitydependent manner between cytoplasmic and Golgi-membrane-localized pools. The related human ARF-GEF protein GBF1 can substitute for garz function in Drosophila tracheal cells, indicating that the relevant functions of these proteins are conserved. We show that garz interacts genetically with the ARF1 homolog ARF79F and with the ARF1-GAP homolog Gap69C, thus placing garz in a regulatory circuit that controls COPI trafficking in Drosophila. Interestingly, ov...

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The Garz Sec7 domain guanine nucleotide exchange factor for Arf regulates salivary gland development in Drosophila

Cited by 23 publications

References 69 publications

GBF1 (Gartenzwerg)-dependent secretion is required for Drosophila tubulogenesis

GBF1 (Gartenzwerg)-dependent secretion is required for Drosophila tubulogenesis

ARF1–GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis

The Drosophila Sec7 domain guanine nucleotide exchange factor protein Gartenzwerg localizes at the cis-Golgi and is essential for epithelial tube expansion

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