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Myosin 18Aα targets the guanine nucleotide exchange factor β‐Pix to the dendritic spines of cerebellar Purkinje neurons and promotes spine maturation
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- Christopher J. Alexander
- Molecular Cell Biology Laboratory Cell and Developmental Biology Center NHLBI NIH Bethesda MD USA
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- Melanie Barzik
- Laboratory of Molecular Genetics NIDCD NIH Bethesda MD USA
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- Ikuko Fujiwara
- Graduate School of Science Osaka City University Osaka Japan
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- Kirsten Remmert
- Surgical Oncology Program NCI NIH Betheda MD USA
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- Ya‐Xian Wang
- Advanced Imaging Core NIDCD NIH Betheda MD USA
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- Ronald S. Petralia
- Advanced Imaging Core NIDCD NIH Betheda MD USA
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- Thomas B. Friedman
- Laboratory of Molecular Genetics NIDCD NIH Bethesda MD USA
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- John A. Hammer
- Molecular Cell Biology Laboratory Cell and Developmental Biology Center NHLBI NIH Bethesda MD USA
Bibliographic Information
- Published
- 2020-12-30
- Resource Type
- journal article
- Rights Information
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1096/fj.202001449r
- Publisher
- Wiley
Search this article
Description
<jats:title>Abstract</jats:title> <jats:p>Myosin 18Aα is a myosin 2‐like protein containing unique N‐ and C‐terminal protein interaction domains that co‐assembles with myosin 2. One protein known to bind to myosin 18Aα is β‐Pix, a guanine nucleotide exchange factor (GEF) for Rac1 and Cdc42 that has been shown to promote dendritic spine maturation by activating the assembly of actin and myosin filaments in spines. Here, we show that myosin 18A⍺ concentrates in the spines of cerebellar Purkinje neurons via co‐assembly with myosin 2 and through an actin binding site in its N‐terminal extension. miRNA‐mediated knockdown of myosin 18A⍺ results in a significant defect in spine maturation that is rescued by an RNAi‐immune version of myosin 18A⍺. Importantly, β‐Pix co‐localizes with myosin 18A⍺ in spines, and its spine localization is lost upon myosin 18A⍺ knockdown or when its myosin 18A⍺ binding site is deleted. Finally, we show that the spines of myosin 18A⍺ knockdown Purkinje neurons contain significantly less F‐actin and myosin 2. Together, these data argue that mixed filaments of myosin 2 and myosin 18A⍺ form a complex with β‐Pix in Purkinje neuron spines that promotes spine maturation by enhancing the assembly of actin and myosin filaments downstream of β‐Pix's GEF activity.</jats:p>
Journal
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- The FASEB Journal
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The FASEB Journal 35 (1), 2020-12-30
Wiley
