Abstract:
:Activation of postsynaptic metabotropic glutamate receptors (mGluRs) modulates neuronal excitability and synaptic plasticity, while deregulation of mGluR signaling has been implicated in neurodevelopmental disorders. Overstimulation of mGluRs is restricted by the rapid endocytosis of receptors after activation. However, how membrane trafficking of mGluRs at synapses is controlled remains poorly defined. We find that in hippocampal neurons, the agonist-induced receptor internalization of synaptic mGluR5 is significantly reduced in Shank knockdown neurons. This is rescued by the re-expression of wild-type Shanks, but not by mutants unable to bind Homer1b/c, Dynamin2, or Cortactin. These effects are paralleled by a reduction in synapses associated with an endocytic zone. Moreover, a mutation in SHANK2 found in autism spectrum disorders (ASDs) similarly disrupts these processes. On the basis of these findings, we propose that synaptic Shank scaffolds anchor the endocytic machinery to govern the efficient trafficking of mGluR5 and to balance the surface expression of mGluRs to efficiently modulate neuronal functioning.
journal_name
Cell Repjournal_title
Cell reportsauthors
Scheefhals N,Catsburg LAE,Westerveld ML,Blanpied TA,Hoogenraad CC,MacGillavry HDdoi
10.1016/j.celrep.2019.08.102subject
Has Abstractpub_date
2019-10-08 00:00:00pages
258-269.e8issue
2issn
2211-1247pii
S2211-1247(19)31164-7journal_volume
29pub_type
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