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LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction

Author

Listed:
  • Jay Penney

    (McGill University)

  • Kazuya Tsurudome

    (McGill University
    Buck Institute for Research on Aging)

  • Edward H. Liao

    (McGill University
    Buck Institute for Research on Aging)

  • Grant Kauwe

    (Buck Institute for Research on Aging)

  • Lindsay Gray

    (Buck Institute for Research on Aging)

  • Akiko Yanagiya

    (Goodman Cancer Research Centre, McGill University, McGill University)

  • Mario R. Calderon

    (McGill University)

  • Nahum Sonenberg

    (Goodman Cancer Research Centre, McGill University, McGill University)

  • A. Pejmun Haghighi

    (McGill University
    Buck Institute for Research on Aging)

Abstract

Parkinson’s disease gene leucine-rich repeat kinase 2 (LRRK2) has been implicated in a number of processes including the regulation of mitochondrial function, autophagy and endocytic dynamics; nevertheless, we know little about its potential role in the regulation of synaptic plasticity. Here we demonstrate that postsynaptic knockdown of the fly homologue of LRRK2 thwarts retrograde, homeostatic synaptic compensation at the larval neuromuscular junction. Conversely, postsynaptic overexpression of either the fly or human LRRK2 transgene induces a retrograde enhancement of presynaptic neurotransmitter release by increasing the size of the release ready pool of vesicles. We show that LRRK2 promotes cap-dependent translation and identify Furin 1 as its translational target, which is required for the synaptic function of LRRK2. As the regulation of synaptic homeostasis plays a fundamental role in ensuring normal and stable synaptic function, our findings suggest that aberrant function of LRRK2 may lead to destabilization of neural circuits.

Suggested Citation

  • Jay Penney & Kazuya Tsurudome & Edward H. Liao & Grant Kauwe & Lindsay Gray & Akiko Yanagiya & Mario R. Calderon & Nahum Sonenberg & A. Pejmun Haghighi, 2016. "LRRK2 regulates retrograde synaptic compensation at the Drosophila neuromuscular junction," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12188
    DOI: 10.1038/ncomms12188
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    Cited by:

    1. Sarah Perry & Yifu Han & Chengjie Qiu & Chun Chien & Pragya Goel & Samantha Nishimura & Manisha Sajnani & Andreas Schmid & Stephan J. Sigrist & Dion Dickman, 2022. "A glutamate receptor C-tail recruits CaMKII to suppress retrograde homeostatic signaling," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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