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Deletion of ATG5 shows a role of autophagy in salivary homeostatic control.

ABSTRACT: Autophagy is a catabolic pathway utilized to maintain a balance among the synthesis, degradation, and recycling of cellular components, thereby playing a role in cell growth, development, and homeostasis. Previous studies revealed that a conditional knockout of essential member(s) of autophagy in a variety of tissues causes changes in structure and function of these tissues. Acinar cell-specific expression of knocked-in Cre recombinase through control of aquaporin 5 (Aqp5) promoter/enhancer (Aqp5-Cre) allows us to specifically inactivate Atg5, a protein necessary for autophagy, in salivary acinar cells of Atg5(f/f);Aqp5-Cre mice. There was no difference in apoptotic or proliferation levels in salivary glands of Atg5/Cre mice from each genotype. However, H&E staining and electron microscopy studies revealed modestly enlarged acinar cells and accumulated secretory granules in salivary glands of Atg5(f/f);Aqp5-Cre mice. Salivary flow rates and amylase contents of Atg5/Cre mice indicated that acinar-specific inactivation of ATG5 did not alter carbachol-evoked saliva and amylase secretion. Conversely, autophagy intersected with salivary morphological and secretory manifestations induced by isoproterenol administration. These results identified a role for autophagy as a homeostasis control in salivary glands. Collectively, Atg5(f/f);Aqp5-Cre mice would be a useful tool to enhance our understanding of autophagy in adaptive responses following targeted head and neck radiation or Sjögren syndrome.

SUBMITTER: Morgan-Bathke M

PROVIDER: S-EPMC3775371 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Deletion of ATG5 shows a role of autophagy in salivary homeostatic control.

Morgan-Bathke M M Lin H H HH Chibly A M AM Zhang W W Sun X X Chen C-H CH Flodby P P Borok Z Z Wu R R Arnett D D Klein R R RR Ann D K DK Limesand K H KH

Journal of dental research 20130724 10

Autophagy is a catabolic pathway utilized to maintain a balance among the synthesis, degradation, and recycling of cellular components, thereby playing a role in cell growth, development, and homeostasis. Previous studies revealed that a conditional knockout of essential member(s) of autophagy in a variety of tissues causes changes in structure and function of these tissues. Acinar cell-specific expression of knocked-in Cre recombinase through control of aquaporin 5 (Aqp5) promoter/enhancer (Aqp ...[more]

PMID: 23884556

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Project description:Synapses and circuits rely on homeostatic forms of regulation in order to transmit meaningful information. The Drosophila melanogaster neuromuscular junction (NMJ) is a well-studied synapse that shows robust homeostatic control of function. Most prior studies of homeostatic plasticity at the NMJ have centered on presynaptic homeostatic potentiation (PHP). PHP happens when postsynaptic muscle neurotransmitter receptors are impaired, triggering retrograde signaling that causes an increase in presynaptic neurotransmitter release. As a result, normal levels of evoked excitation are maintained. The counterpart to PHP at the NMJ is presynaptic homeostatic depression (PHD). Overexpression of the Drosophila vesicular glutamate transporter (VGlut) causes an increase in the amplitude of spontaneous events. PHD happens when the synapse responds to the challenge by decreasing quantal content (QC) during evoked neurotransmissionagain, resulting in normal levels of postsynaptic excitation. We hypothesized that there may exist a class of molecules that affects both PHP and PHD. Impairment of any such molecule could hurt a synapses ability to respond to any significant homeostatic challenge. We conducted an electrophysiology-based screen for blocks of PHD. We did not observe a block of PHD in the genetic conditions screened, but we found loss-of-function conditions that led to a substantial deficit in evoked amplitude when combined with VGlut overexpression. The conditions causing this phenotype included a double heterozygous loss-of-function condition for genes encoding the inositol trisphosphate receptor (IP3R itpr) and ryanodine receptor (RyR). IP3Rs and RyRs gate calcium release from intracellular stores. Pharmacological agents targeting IP3R and RyR recapitulated the genetic losses of these factors, as did lowering calcium levels from other sources. Our data are consistent with the idea that the homeostatic signaling process underlying PHD is especially sensitive to levels of calcium at the presynapse.

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Deletion of ATG5 shows a role of autophagy in salivary homeostatic control.

Publications

Deletion of ATG5 shows a role of autophagy in salivary homeostatic control.

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