RT Journal Article
SR Electronic
T1 Surfaceome dynamics during neuronal development and synaptic plasticity reveal system-wide surfaceome reorganization independent of global proteostasis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 731083
DO 10.1101/731083
A1 Marc van Oostrum
A1 Benjamin Campbell
A1 Maik Müller
A1 Patrick G. A. Pedrioli
A1 Shiva K. Tyagarajan
A1 Bernd Wollscheid
YR 2019
UL http://biorxiv.org/content/early/2019/08/15/731083.abstract
AB Neurons are highly compartmentalized cells with tightly controlled subcellular protein organization. While broad brain transcriptome, connectome and global proteome maps are being generated, system-wide analysis of temporal protein dynamics at the subcellular level are currently lacking for neuronal development and synapse formation. We performed a temporally-resolved surfaceome analysis of developing primary neuron cultures to a depth of 1000 bona fide surface proteins and reveal dynamic surface protein clusters that reflect the functional requirements during distinct stages of neuronal development. Moreover, our data shows that synaptic proteins are globally trafficked to the surface prior to synapse formation. Direct comparison of surface and total protein pools demonstrates that, depending on the time scale, surface abundance changes can correlate or differ from total protein abundance. The uncoupling of surface and total abundance changes has direct functional implications as shown in the context of synaptic vesicle transport. To demonstrate the utility of our approach we analyzed the surfaceome modulation in response to homeostatic synaptic scaling and found dynamic remodeling of the neuronal surface, which was largely independent of global proteostasis, indicative of wide-spread regulation on the level of surface trafficking. Finally, we present a quantitative analysis of the neuronal surface during early-phase long-term potentiation (LTP) and reveal fast externalization of diverse classes of surface proteins beyond the AMPA receptor, providing new insights into the requirement of exocytosis for LTP. Our resource and finding of organizational principles highlight the importance of subcellular resolution for systems-level understanding of cellular processes, which are typically masked by broad omics-style approaches.