Format

Send to

Choose Destination
Cell. 2018 Jul 25. pii: S0092-8674(18)30850-X. doi: 10.1016/j.cell.2018.06.047. [Epub ahead of print]

Reconstituted Postsynaptic Density as a Molecular Platform for Understanding Synapse Formation and Plasticity.

Author information

1
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
2
Department of Physics, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
3
Department of Physics, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
4
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: mzhang@ust.hk.

Abstract

Synapses are semi-membraneless, protein-dense, sub-micron chemical reaction compartments responsible for signal processing in each and every neuron. Proper formation and dynamic responses to stimulations of synapses, both during development and in adult, are fundamental to functions of mammalian brains, although the molecular basis governing formation and modulation of compartmentalized synaptic assemblies is unclear. Here, we used a biochemical reconstitution approach to show that, both in solution and on supported membrane bilayers, multivalent interaction networks formed by major excitatory postsynaptic density (PSD) scaffold proteins led to formation of PSD-like assemblies via phase separation. The reconstituted PSD-like assemblies can cluster receptors, selectively concentrate enzymes, promote actin bundle formation, and expel inhibitory postsynaptic proteins. Additionally, the condensed phase PSD assemblies have features that are distinct from those in homogeneous solutions and fit for synaptic functions. Thus, we have built a molecular platform for understanding how neuronal synapses are formed and dynamically regulated.

KEYWORDS:

biochemical reconstitution; biomolecular condensates; membraneless organelle; phase separation; postsynaptic density; scaffold proteins; synapse formation; synaptic signaling

PMID:
30078712
DOI:
10.1016/j.cell.2018.06.047

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center