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Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.

Publication ,  Journal Article
Maynard, JC; Pham, T; Zheng, T; Jockheck-Clark, A; Rankin, HB; Newgard, CB; Spana, EP; Nicchitta, CV
Published in: Dev Biol
March 15, 2010

GRP94, the endoplasmic reticulum Hsp90, is a metazoan-restricted chaperone essential for early development in mammals, yet dispensable for mammalian cell viability. This dichotomy suggests that GRP94 is required for the functional expression of secretory and/or membrane proteins that enable the integration of cells into tissues. To explore this hypothesis, we have identified the Drosophila ortholog of GRP94, Gp93, and report that Gp93 is an essential gene in Drosophila. Loss of zygotic Gp93 expression is late larval-lethal and causes prominent defects in the larval midgut, the sole endoderm-derived larval tissue. Gp93 mutant larvae display pronounced defects in the midgut epithelium, with aberrant copper cell structure, markedly reduced gut acidification, atypical septate junction structure, depressed gut motility, and deficits in intestinal nutrient uptake. The metabolic consequences of the loss of Gp93-expression are profound; Gp93 mutant larvae exhibit a starvation-like metabolic phenotype, including suppression of insulin signaling and extensive mobilization of amino acids and triglycerides. The defects in copper cell structure/function accompanying loss of Gp93 expression resemble those reported for mutations in labial, an endodermal homeotic gene required for copper cell specification, and alpha-spectrin, thus suggesting an essential role for Gp93 in the functional expression of secretory/integral membrane protein-encoding lab protein target genes and/or integral membrane protein(s) that interact with the spectrin cytoskeleton to confer epithelial membrane specialization.

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Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

March 15, 2010

Volume

339

Issue

2

Start / End Page

295 / 306

Location

United States

Related Subject Headings

  • Mutation
  • Molecular Chaperones
  • Membrane Proteins
  • Larva
  • Intestinal Mucosa
  • Homeostasis
  • HSP70 Heat-Shock Proteins
  • Epithelial Cells
  • Embryo, Nonmammalian
  • Drosophila Proteins
 

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Maynard, J. C., Pham, T., Zheng, T., Jockheck-Clark, A., Rankin, H. B., Newgard, C. B., … Nicchitta, C. V. (2010). Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control. Dev Biol, 339(2), 295–306. https://doi.org/10.1016/j.ydbio.2009.12.023
Maynard, Jason C., Trang Pham, Tianli Zheng, Angela Jockheck-Clark, Helen B. Rankin, Christopher B. Newgard, Eric P. Spana, and Christopher V. Nicchitta. “Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.Dev Biol 339, no. 2 (March 15, 2010): 295–306. https://doi.org/10.1016/j.ydbio.2009.12.023.
Maynard JC, Pham T, Zheng T, Jockheck-Clark A, Rankin HB, Newgard CB, et al. Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control. Dev Biol. 2010 Mar 15;339(2):295–306.
Maynard, Jason C., et al. “Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.Dev Biol, vol. 339, no. 2, Mar. 2010, pp. 295–306. Pubmed, doi:10.1016/j.ydbio.2009.12.023.
Maynard JC, Pham T, Zheng T, Jockheck-Clark A, Rankin HB, Newgard CB, Spana EP, Nicchitta CV. Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control. Dev Biol. 2010 Mar 15;339(2):295–306.
Journal cover image

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

March 15, 2010

Volume

339

Issue

2

Start / End Page

295 / 306

Location

United States

Related Subject Headings

  • Mutation
  • Molecular Chaperones
  • Membrane Proteins
  • Larva
  • Intestinal Mucosa
  • Homeostasis
  • HSP70 Heat-Shock Proteins
  • Epithelial Cells
  • Embryo, Nonmammalian
  • Drosophila Proteins