Molecular Dissection of Neurobeachin Function at Excitatory Synapses

Frontiers in Synaptic Neuroscience
Daniele RepettoMarkus Missler

Abstract

Spines are small protrusions from dendrites where most excitatory synapses reside. Changes in number, shape, and size of dendritic spines often reflect changes of neural activity in entire circuits or at individual synapses, making spines key structures of synaptic plasticity. Neurobeachin is a multidomain protein with roles in spine formation, postsynaptic neurotransmitter receptor targeting and actin distribution. However, the contributions of individual domains of Neurobeachin to these functions is poorly understood. Here, we used mostly live cell imaging and patch-clamp electrophysiology to monitor morphology and function of spinous synapses in primary hippocampal neurons. We demonstrate that a recombinant full-length Neurobeachin from humans can restore mushroom spine density and excitatory postsynaptic currents in neurons of Neurobeachin-deficient mice. We then probed the role of individual domains of Neurobeachin by comparing them to the full-length molecule in rescue experiments of knockout neurons. We show that the combined PH-BEACH domain complex is highly localized in spine heads, and that it is sufficient to restore normal spine density and surface targeting of postsynaptic AMPA receptors. In addition, we report tha...Continue Reading

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Citations

May 26, 2021·Current Biology : CB·Jayne Aiken, Erika L F Holzbaur
Aug 21, 2021·Molecular Genetics and Metabolism·Thomas BoulinStephen C Pak

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Datasets Mentioned

BETA
100069291

Methods Mentioned

BETA
transfection
profiler
confocal microscopy
PCR
surface plasmon resonance

Software Mentioned

Minianalysis
Excel
BEACH
PH
Patchmaster
phyre2
Clampex
Nbea
GraphPad Prism
ImageJ

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