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Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis

Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among the septins, septin7 (SEPT7) is an important component of all septin filaments. Here we show that protein kinase A (PKA) phosphorylates SEPT7 at Thr197, thus disrupting septin filament dynami...

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Autores principales: Wang, Han-Yu, Lin, Chun-Hsiang, Shen, Yi-Ru, Chen, Ting-Yu, Wang, Chia-Yih, Kuo, Pao-Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916176/
https://www.ncbi.nlm.nih.gov/pubmed/33572403
http://dx.doi.org/10.3390/cells10020361
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author Wang, Han-Yu
Lin, Chun-Hsiang
Shen, Yi-Ru
Chen, Ting-Yu
Wang, Chia-Yih
Kuo, Pao-Lin
author_facet Wang, Han-Yu
Lin, Chun-Hsiang
Shen, Yi-Ru
Chen, Ting-Yu
Wang, Chia-Yih
Kuo, Pao-Lin
author_sort Wang, Han-Yu
collection PubMed
description Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among the septins, septin7 (SEPT7) is an important component of all septin filaments. Here we show that protein kinase A (PKA) phosphorylates SEPT7 at Thr197, thus disrupting septin filament dynamics and ciliogenesis. The Thr197 residue of SEPT7, a PKA phosphorylating site, was conserved among different species. Treatment with cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation, followed by disruption of septin filament formation. Constitutive phosphorylation of SEPT7 at Thr197 reduced SEPT7‒SEPT7 interaction, but did not affect SEPT7‒SEPT6‒SEPT2 or SEPT4 interaction. Moreover, we noted that SEPT7 interacted with PKACA2 via its GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.
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spelling pubmed-79161762021-03-01 Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis Wang, Han-Yu Lin, Chun-Hsiang Shen, Yi-Ru Chen, Ting-Yu Wang, Chia-Yih Kuo, Pao-Lin Cells Article Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among the septins, septin7 (SEPT7) is an important component of all septin filaments. Here we show that protein kinase A (PKA) phosphorylates SEPT7 at Thr197, thus disrupting septin filament dynamics and ciliogenesis. The Thr197 residue of SEPT7, a PKA phosphorylating site, was conserved among different species. Treatment with cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation, followed by disruption of septin filament formation. Constitutive phosphorylation of SEPT7 at Thr197 reduced SEPT7‒SEPT7 interaction, but did not affect SEPT7‒SEPT6‒SEPT2 or SEPT4 interaction. Moreover, we noted that SEPT7 interacted with PKACA2 via its GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation. MDPI 2021-02-09 /pmc/articles/PMC7916176/ /pubmed/33572403 http://dx.doi.org/10.3390/cells10020361 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Han-Yu
Lin, Chun-Hsiang
Shen, Yi-Ru
Chen, Ting-Yu
Wang, Chia-Yih
Kuo, Pao-Lin
Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis
title Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis
title_full Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis
title_fullStr Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis
title_full_unstemmed Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis
title_short Protein Kinase A-Mediated Septin7 Phosphorylation Disrupts Septin Filaments and Ciliogenesis
title_sort protein kinase a-mediated septin7 phosphorylation disrupts septin filaments and ciliogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916176/
https://www.ncbi.nlm.nih.gov/pubmed/33572403
http://dx.doi.org/10.3390/cells10020361
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