PgmNr D1225: Metabolic role of GABA in the blood progenitors.

Authors:
M. Shin; J. Shim


Institutes
Hanyang University, Seoul, KR.


Keyword: hematopoietic stem cells

Abstract:

 Drosophila hematopoietic organ called Lymph gland is well known for its intrinsic and extrinsic controls in the maintenance of blood progenitors. Previous study has identified GABA as a novel systemic factor that regulates the blood progenitor maintenance through changes in cytosolic calcium concentration. GABA is released from a subset of neuroendocrine cells in the brain of which secretion is mainly controlled by the olfactory receptor neurons (ORNs). When GABA secretion is decreased, blood progenitors are differentiated as cytosolic calcium, a downstream of GABAB receptor in the blood progenitors, is down-regulated. However, whether excessive GABA influences the blood progenitor of Drosophila has not been described. Here, we found that constitutive activation of ORNs is enough to release excessive GABA from the brain that also interferes with the blood progenitor maintenance. Excessive systemic GABA increases the level of reactive oxygen species (ROS) in the blood that in turn results in the precocious differentiation of blood cells. Interestingly, this phenotype is rescued by changes in the TCA cycle, indicating a tight link between the systemic GABA and metabolic changes in the blood cells. Overall, our work highlights the novel function of an unconventional TCA-cycle that couples in part with a shunt pathway and its importance in the fine balance of ROS in the blood progenitors.

*This work was supported by NRF-2014S1A2A2028388 and NRF-2014R1A1A1002685.