Abstract
ABSTRACTDrosophila CrebA facilitates high-level secretion by transcriptional upregulation of the protein components of the core secretory machinery. In CrebA mutant embryos, both salivary gland (SG) morphology and epidermal cuticle secretion are abnormal, phenotypes similar to those observed with mutations in core secretory pathway component genes. Here, we examine the cellular defects associated with CrebA loss in the SG epithelium. Apically localized secretory vesicles are smaller and less abundant, consistent with overall reductions in secretion. Unexpectedly, global mislocalization of cellular organelles and excess membrane accumulation in the septate junctions (SJs) are also observed. Whereas mutations in core secretory pathway genes lead to organelle localization defects similar to those of CrebA mutants, they have no effect on SJ-associated membrane. Mutations in tetraspanin genes, which are normally repressed by CrebA, have mild defects in SJ morphology that are rescued by simultaneous CrebA loss. Correspondingly, removal of several tetraspanins gives partial rescue of the CrebA SJ phenotype, supporting a role for tetraspanins in SJ organization.
Highlights
Development of multicellular organisms requires the specialization of a myriad of cell types, each providing unique functional capabilities
To examine defects associated with CrebA loss at the cellular level, the abundance and distribution of proteins associated with secretory and non-secretory organelles were analyzed by confocal microscopy
Whereas in wild-type (WT) salivary gland (SG) cells, mtTFA mitochondrial transcription factor staining was evenly distributed at very low levels throughout the cell, in CrebA mutant SGs, mtTFA staining was concentrated in a small subcellular domain, most often found in an apical region (Fig. 1A)
Summary
Development of multicellular organisms requires the specialization of a myriad of cell types, each providing unique functional capabilities. Among the specializations of epithelial cells is the capacity to synthesize and secrete high levels of proteins and other substances. The Drosophila salivary gland has proven an excellent model system for learning how epithelial organs achieve both the proper architecture and physiological adaptations for secretion (Chung et al, 2014). The Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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