A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex
Myosin Va (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but the role of MyoVa in synaptic development and function is largely unknown. Here, in studies using the dominantnegative MyoVa neurological mutant mouse F...
| Main Authors: | , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Published: |
Society for Neuroscience
2017
|
| Online Access: | http://hdl.handle.net/1721.1/112239 https://orcid.org/0000-0003-4308-7073 https://orcid.org/0000-0003-2268-0863 |
| _version_ | 1811091715182821376 |
|---|---|
| author | van Zundert, B. Yoshii, Akira Zhao, Jian-Ping Pandian, Swarna Constantine-Paton, Martha |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences van Zundert, B. Yoshii, Akira Zhao, Jian-Ping Pandian, Swarna Constantine-Paton, Martha |
| author_sort | van Zundert, B. |
| collection | MIT |
| description | Myosin Va (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but the role of MyoVa in synaptic development and function is largely unknown. Here, in studies using the dominantnegative MyoVa neurological mutant mouse Flailer, we find that MyoVa plays an essential role in activity-dependent delivery of PSD-95 and other critical PSD molecules to synapses and in endocytosis of AMPA-type glutamate receptors (AMPAR) in the dendrites of CNS neurons. MyoVa is known to carry a complex containing the major scaffolding proteins of the mature PSD, PSD-95, SAPAP1/GKAP, Shank, and Homer to dendritic spine synapses. In Flailer, neurons show abnormal dendritic shaft localization of PSD-95, stargazin, dynamin3, AMPARs and abnormal spine morphology. Flailer neurons also have abnormally highAMPARminiature current frequencies and spontaneous AMPAR currents that are more frequent and larger than in wild-type while numbers of NMDAR containing synapses remain normal. The AMPAR abnormalities are consistent with a severely disrupted developmental regulation of long-term depression that we find in cortical Flailer neurons. Thus MyoVa plays a fundamentally important role both in localizing mature glutamate synapses to spines and in organizing the synapse for normal function. For this reason Flailer mice will be valuable in further dissecting the role of MyoVa in normal synaptic and circuit refinement and also in studies of neurological and neuropsychiatric diseases where disruptions of normal glutamate synapses are frequently observed. |
| first_indexed | 2024-09-23T15:06:50Z |
| format | Article |
| id | mit-1721.1/112239 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:06:50Z |
| publishDate | 2017 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/1122392022-09-29T12:49:02Z A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex van Zundert, B. Yoshii, Akira Zhao, Jian-Ping Pandian, Swarna Constantine-Paton, Martha Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Yoshii, Akira Zhao, Jian-Ping Pandian, Swarna Constantine-Paton, Martha Myosin Va (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but the role of MyoVa in synaptic development and function is largely unknown. Here, in studies using the dominantnegative MyoVa neurological mutant mouse Flailer, we find that MyoVa plays an essential role in activity-dependent delivery of PSD-95 and other critical PSD molecules to synapses and in endocytosis of AMPA-type glutamate receptors (AMPAR) in the dendrites of CNS neurons. MyoVa is known to carry a complex containing the major scaffolding proteins of the mature PSD, PSD-95, SAPAP1/GKAP, Shank, and Homer to dendritic spine synapses. In Flailer, neurons show abnormal dendritic shaft localization of PSD-95, stargazin, dynamin3, AMPARs and abnormal spine morphology. Flailer neurons also have abnormally highAMPARminiature current frequencies and spontaneous AMPAR currents that are more frequent and larger than in wild-type while numbers of NMDAR containing synapses remain normal. The AMPAR abnormalities are consistent with a severely disrupted developmental regulation of long-term depression that we find in cortical Flailer neurons. Thus MyoVa plays a fundamentally important role both in localizing mature glutamate synapses to spines and in organizing the synapse for normal function. For this reason Flailer mice will be valuable in further dissecting the role of MyoVa in normal synaptic and circuit refinement and also in studies of neurological and neuropsychiatric diseases where disruptions of normal glutamate synapses are frequently observed. National Institutes of Health (U.S.) (Grant R01-EY014074–17) National Institutes of Health (U.S.) (Grant EY014420) 2017-11-20T16:38:08Z 2017-11-20T16:38:08Z 2013-05 2013-03 2017-11-01T18:39:46Z Article http://purl.org/eprint/type/JournalArticle 0270-6474 1529-2401 http://hdl.handle.net/1721.1/112239 Yoshii, A. et al. “A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex.” Journal of Neuroscience 33, 19 (May 2013): 8472–8482 © 2013 The Author(s) https://orcid.org/0000-0003-4308-7073 https://orcid.org/0000-0003-2268-0863 http://dx.doi.org/10.1523/JNEUROSCI.4585-12.2013 Journal of Neuroscience Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Society for Neuroscience Society for Neuroscience |
| spellingShingle | van Zundert, B. Yoshii, Akira Zhao, Jian-Ping Pandian, Swarna Constantine-Paton, Martha A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex |
| title | A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex |
| title_full | A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex |
| title_fullStr | A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex |
| title_full_unstemmed | A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex |
| title_short | A Myosin Va Mutant Mouse with Disruptions in Glutamate Synaptic Development and Mature Plasticity in Visual Cortex |
| title_sort | myosin va mutant mouse with disruptions in glutamate synaptic development and mature plasticity in visual cortex |
| url | http://hdl.handle.net/1721.1/112239 https://orcid.org/0000-0003-4308-7073 https://orcid.org/0000-0003-2268-0863 |
| work_keys_str_mv | AT vanzundertb amyosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT yoshiiakira amyosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT zhaojianping amyosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT pandianswarna amyosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT constantinepatonmartha amyosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT vanzundertb myosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT yoshiiakira myosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT zhaojianping myosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT pandianswarna myosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex AT constantinepatonmartha myosinvamutantmousewithdisruptionsinglutamatesynapticdevelopmentandmatureplasticityinvisualcortex |