PUBLICATION

GABA-A receptor and mitochondrial TSPO signaling act in parallel to regulate melanocyte stem cell quiescence in larval zebrafish

Authors
Allen, J.R., Skeath, J.B., Johnson, S.L.
ID
ZDB-PUB-191024-5
Date
2019
Source
Pigment cell & melanoma research   33(3): 416-425 (Journal)
Registered Authors
Johnson, Stephen L.
Keywords
GABA-A, Melanocyte, TSPO, stem cell, zebrafish
MeSH Terms
  • Stem Cells/cytology*
  • Stem Cells/drug effects
  • Stem Cells/metabolism
  • Receptors, GABA-A/metabolism*
  • Mitochondria/drug effects
  • Mitochondria/metabolism*
  • Receptors, GABA/metabolism*
  • Cell Cycle*/drug effects
  • Melanocytes/cytology*
  • Melanocytes/drug effects
  • Calcium Signaling/drug effects
  • Larva/drug effects
  • Animals
  • Zebrafish/metabolism*
  • GABA-A Receptor Antagonists/pharmacology
  • Signal Transduction*/drug effects
  • Ligands
  • Calcium/metabolism
  • Zebrafish Proteins/metabolism*
  • Gluconeogenesis/drug effects
(all 20)
PubMed
31642595 Full text @ Pigment Cell Melanoma Res.
Abstract
Tissue regeneration and homeostasis often require recruitment of undifferentiated precursors (adult stem cells; ASCs). While many ASCs continuously proliferate throughout the lifetime of an organism, others are recruited from a quiescent state to replenish their target tissue. A longstanding question in stem cell biology concerns how long-lived, non-dividing ASCs regulate the transition between quiescence and proliferation. We study the melanocyte stem cell (MSC) to investigate the molecular pathways that regulate ASC quiescence. Our prior work indicated that GABA-A receptor activation promotes MSC quiescence in larval zebrafish. Here, through pharmacological and genetic approaches we show that GABA-A acts through calcium signaling to maintain MSC quiescence. Unexpectedly, we identified translocator protein (TSPO), a mitochondrial membrane associated protein that regulates mitochondrial function and metabolic homeostasis, as a parallel regulator of MSC quiescence. We found that both TSPO-specific ligands and induction of gluconeogenesis likely act in the same pathway to promote MSC activation and melanocyte production in larval zebrafish. In contrast, TSPO and gluconeogenesis appear to act in parallel to GABA-A receptor signaling to regulate MSC quiescence and vertebrate pigment patterning.
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Orthology
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Marker Marker Type Name
GFPEFGGFP
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Citation
Allen, J.R., Skeath, J.B., Johnson, S.L. (2019) GABA-A receptor and mitochondrial TSPO signaling act in parallel to regulate melanocyte stem cell quiescence in larval zebrafish. Pigment cell & melanoma research. 33(3):416-425.