Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.

The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spine...

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Main Authors: Devyn Oliver, Shankar Ramachandran, Alison Philbrook, Christopher M Lambert, Ken C Q Nguyen, David H Hall, Michael M Francis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS Genetics
Online Access:https://doi.org/10.1371/journal.pgen.1010016
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author Devyn Oliver
Shankar Ramachandran
Alison Philbrook
Christopher M Lambert
Ken C Q Nguyen
David H Hall
Michael M Francis
author_facet Devyn Oliver
Shankar Ramachandran
Alison Philbrook
Christopher M Lambert
Ken C Q Nguyen
David H Hall
Michael M Francis
author_sort Devyn Oliver
collection DOAJ
description The functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons. We show that the presynaptic adhesion protein neurexin/NRX-1 is required for stabilization of postsynaptic structure. We find that early postsynaptic developmental events proceed without a strict requirement for synaptic activity and are not disrupted by deletion of neurexin/nrx-1. However, in the absence of presynaptic NRX-1, dendritic spines and receptor clusters become destabilized and collapse prior to adulthood. We demonstrate that NRX-1 delivery to presynaptic terminals is dependent on kinesin-3/UNC-104 and show that ongoing UNC-104 function is required for postsynaptic maintenance in mature animals. By defining the dynamics and temporal order of synapse formation and maintenance events in vivo, we describe a mechanism for stabilizing mature circuit connectivity through neurexin-based adhesion.
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spelling doaj.art-1e2825cd57174bc1afbb64da02697e422022-12-22T02:32:43ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042022-01-01181e101001610.1371/journal.pgen.1010016Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.Devyn OliverShankar RamachandranAlison PhilbrookChristopher M LambertKen C Q NguyenDavid H HallMichael M FrancisThe functional properties of neural circuits are defined by the patterns of synaptic connections between their partnering neurons, but the mechanisms that stabilize circuit connectivity are poorly understood. We systemically examined this question at synapses onto newly characterized dendritic spines of C. elegans GABAergic motor neurons. We show that the presynaptic adhesion protein neurexin/NRX-1 is required for stabilization of postsynaptic structure. We find that early postsynaptic developmental events proceed without a strict requirement for synaptic activity and are not disrupted by deletion of neurexin/nrx-1. However, in the absence of presynaptic NRX-1, dendritic spines and receptor clusters become destabilized and collapse prior to adulthood. We demonstrate that NRX-1 delivery to presynaptic terminals is dependent on kinesin-3/UNC-104 and show that ongoing UNC-104 function is required for postsynaptic maintenance in mature animals. By defining the dynamics and temporal order of synapse formation and maintenance events in vivo, we describe a mechanism for stabilizing mature circuit connectivity through neurexin-based adhesion.https://doi.org/10.1371/journal.pgen.1010016
spellingShingle Devyn Oliver
Shankar Ramachandran
Alison Philbrook
Christopher M Lambert
Ken C Q Nguyen
David H Hall
Michael M Francis
Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.
PLoS Genetics
title Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.
title_full Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.
title_fullStr Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.
title_full_unstemmed Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.
title_short Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components.
title_sort kinesin 3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components
url https://doi.org/10.1371/journal.pgen.1010016
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