The International Journal of Developmental Biology

Int. J. Dev. Biol. 64: 289 - 297 (2020)

Vol 64, Issue 4-5-6

Special Issue: Developmental Biology in India - Second Part

Drosophila Mon1 and Rab7 interact to regulate glutamate receptor levels at the neuromuscular junction

Published: 23 June 2020

Anagha Basargekar1, Shweta Yogi1, Zeeshan Mushtaq2, Senthilkumar Deivasigamani3, Vimlesh Kumar2, Girish S. Ratnaparkhi3 and Anuradha Ratnaparkhi*,1

1Agharkar Research Institute, Pune, 2Indian Institute of Science Education and Research, Bhopal and 3Indian Institute of Science Education and Research, Pune, India


Regulation of post-synaptic receptors plays an important role in determining synaptic strength and plasticity. The Drosophila larval neuromuscular junction (nmj) has been used extensively as a model to understand some of these processes. In this context, we are interested in the role of Drosophila Monensin sensitivity protein 1 (DMon1) in regulating glutamate receptor (GluRIIA) levels at the nmj. DMon1 is an evolutionarily conserved protein which, in complex with calcium caffeine zinc sensitivity1 (CCZ1), regulates the conversion of early endosomes to late endosomes through recruitment of Rab7. C-terminal deletion mutants of Dmon1 (Dmon1Δ181) exhibit lethality. The escapers have a short life span and exhibit severe motor defects. At the nmj, these mutants show defects in synaptic morphology and a strong increase in GluRIIA levels. The mechanism by which Dmon1 regulates GluRIIA is unclear. In this study, we have characterized an EMS mutant referred to as pog1 and demonstrate it to be an allele of Dmon1. Further, we have examined the role of rab7 in regulating GluRIIA. We show that similar to Dmon1, knock-down of rab7 using RNAi in neurons, but not muscles, leads to an increase in GluRIIA. Loss of one copy each of Dmon1 and rab7 leads to a synergistic increase in receptor expression. Further, overexpression of an activated Rab7 can rescue the GluRIIA phenotype observed in Dmon1Δ181 mutants. Together, these results highlight a neuronal role for Rab7 in GluRIIA regulation and underscore the importance of the endo-lysosomal pathway in this process.


Dmon1, Rab7, GluRIIA, nmj, Drosophila

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