Jun Wu Ph.D student 18th July 2016

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Presentation transcript:

Jun Wu Ph.D student wudream@seu.edu.cn 18th July 2016 Proteolytic maturation of Drosophila Neuroligin3 by TACE regulates locomotor activity Jun Wu Ph.D student wudream@seu.edu.cn 18th July 2016

Protein ectodomain shedding and signal transduction J. Scheller et al., Trends Immunol (2011)

Classical examples of protein cleavage APP signaling Notching signaling H. Wang et al., Trends Pharmacol Sci (2013) M. E. Fortini, Developmental cell (2009)

Proteolytic cleavage of autism-associated Nlgs R. T. Peixoto et al., Neuron (2012) K. Suzuki et al., Neuron (2012) C. Betancur et al., Trends Neurosci (2009) Community Report on Autism • 2014 S. S. Mitra et al., Cell (2015)

The highlight of our study

dnlg3 mutants exhibit reduced locomotor activity Giorgio F Gilestro. Nat protoc. (2012)

Neuronal DNlg3 undergoes proteolytic cleavage B C

DNlg3 is cleaved by TACE in vivo and in vitro

Genetation of tace mutant by CRISPR-Cas9 D

tace mutants show similar inactivity phenotype B

DNlg3 is cleaved at AchE-like domain during A522 and N532 region B D

DNlg3 is cleaved by TACE intracellularly HA-DNlg3 D DNlg3 TACE DNlg3 TACE DAPI DNlg3 TACE

DNlg3 is cleaved at Golgi apparatus B (ER) (Golgi)

DNlg3 cleavage is essential for locomotor activity

Working model

Acknowledgements Wei Xie lab http://webplus.seu.edu.cn/_s222/12560/list.psp

Thanks for your attention!