Nanoscope odyssey into the presynapse

A.T. Bademosi,^1,3 R. Kasula,^1,3 M. Joensuu,^1,3 A. Papadopulos,^1,3 E. Lauwers,² P. Padmanabhan,^3,4 A. Papadopulos,¹ G.J. Goodhill,^3,4 P. Verstreken,² B. van Swinderen³ and F.A. Meunier,^1,3 ¹Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia, ²VIB Center for the Biology of Disease, and Department for Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium, ³Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia and ⁴School of Mathematics and Physics, The University of Queensland, St Lucia, QLD 4072, Australia.

With the advent of super-resolution microscopy, the door is now opened to dissect the mechanism of neurotransmitter release using nanoscale imaging techniques. We demonstrate in neurosecretory cells that Munc18-1, a key presynaptic protein, controls the engagement of Syntaxin1A into the SNARE complex via the opening of a critical hinge loop in domain 3A (Kasula et al., 2016). We then turn to the drosophila synapse to demonstrate that syntaxin1A forms nanoclusters which are dynamically regulated during neurotransmitter release by poly-phosphoinositides and NSF-dependent SNARE disassembly (Bademosi et al., 2016). Finally, we venture into the hippocampal presynapse to establish the first technique capable of imaging single synaptic vesicles in the crowded environment of the hippocampal synapse. Our results reveal that synaptic vesicles dynamically oscillate between several diffusion states with distinct rates of transition between these states (Joensuu et al., 2016).

Kasula R, Chai YJ, Bademosi AT, Harper CB, Gormal RS, Morrow IC, Hosy E, Collins BM, Choquet D, Papadopulos A, Meunier FA. (2016) The Munc18-1 domain 3a hinge-loop controls syntaxin-1A nanodomain assembly and engagement with the SNARE complex during secretory vesicle priming. J Cell Biol 214, 847-58.

Bademosi AT, Lauwers E, Padmanabhan P, Odierna L, Chai YJ, Papadopulos A, Goodhill GJ, Verstreken P, van Swinderen B, Meunier FA. (2016) In vivo single molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent reversible trapping in presynaptic nanoclusters. Nat Commun [Accepted 24.09.2016].

Joensuu M, Padmanabhan P, Durisic N, Bademosi AT, Cooper-Williams L, Morrow IC, Harper CB, Jung W, Parton RG, Goodhill GJ, Papadopulos A, Meunier FA. (2016) Sub-diffractional tracking of internalized molecules reveals heterogeneous motion states of synaptic vesicles. J Cell Biol [Accepted 22.09.2016].