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

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Feb 12

PMID 33572403

Citations 4

Authors

Han-Yu Wang

Chun-Hsiang Lin

Yi-Ru Shen

Ting-Yu Chen

Chia-Yih Wang

Pao-Lin Kuo

Affiliations

Soon will be listed here.

Abstract

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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References

Li S, Ou X, Wei L, Wang Z, Zhang Q, Ouyang Y . Septin 7 is required for orderly meiosis in mouse oocytes. Cell Cycle. 2012; 11(17):3211-8. PMC: 3466520. DOI: 10.4161/cc.21553. View

Hildebrandt F, Benzing T, Katsanis N . Ciliopathies. N Engl J Med. 2011; 364(16):1533-43. PMC: 3640822. DOI: 10.1056/NEJMra1010172. View

Ewers H, Tada T, Petersen J, Racz B, Sheng M, Choquet D . A Septin-Dependent Diffusion Barrier at Dendritic Spine Necks. PLoS One. 2014; 9(12):e113916. PMC: 4262254. DOI: 10.1371/journal.pone.0113916. View

Xue J, Wang X, Malladi C, Kinoshita M, Milburn P, Lengyel I . Phosphorylation of a new brain-specific septin, G-septin, by cGMP-dependent protein kinase. J Biol Chem. 2000; 275(14):10047-56. DOI: 10.1074/jbc.275.14.10047. View

Garcia 3rd G, Bertin A, Li Z, Song Y, McMurray M, Thorner J . Subunit-dependent modulation of septin assembly: budding yeast septin Shs1 promotes ring and gauze formation. J Cell Biol. 2011; 195(6):993-1004. PMC: 3241732. DOI: 10.1083/jcb.201107123. View

Hu Q, Milenkovic L, Jin H, Scott M, Nachury M, Spiliotis E . A septin diffusion barrier at the base of the primary cilium maintains ciliary membrane protein distribution. Science. 2010; 329(5990):436-9. PMC: 3092790. DOI: 10.1126/science.1191054. View

Keeling J, Tsiokas L, Maskey D . Cellular Mechanisms of Ciliary Length Control. Cells. 2016; 5(1). PMC: 4810091. DOI: 10.3390/cells5010006. View

Mostowy S, Cossart P . Septins: the fourth component of the cytoskeleton. Nat Rev Mol Cell Biol. 2012; 13(3):183-94. DOI: 10.1038/nrm3284. View

Sirajuddin M, Farkasovsky M, Hauer F, Kuhlmann D, Macara I, Weyand M . Structural insight into filament formation by mammalian septins. Nature. 2007; 449(7160):311-5. DOI: 10.1038/nature06052. View

10.

Kim S, Shindo A, Park T, Oh E, Ghosh S, Gray R . Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science. 2010; 329(5997):1337-40. PMC: 3509789. DOI: 10.1126/science.1191184. View

11.

Dolat L, Hu Q, Spiliotis E . Septin functions in organ system physiology and pathology. Biol Chem. 2013; 395(2):123-41. PMC: 4452026. DOI: 10.1515/hsz-2013-0233. View

12.

Estey M, Di Ciano-Oliveira C, Froese C, Bejide M, Trimble W . Distinct roles of septins in cytokinesis: SEPT9 mediates midbody abscission. J Cell Biol. 2010; 191(4):741-9. PMC: 2983063. DOI: 10.1083/jcb.201006031. View

13.

Lin Y, Kuo Y, Chiang H, Kuo P . The role of the septin family in spermiogenesis. Spermatogenesis. 2012; 1(4):298-302. PMC: 3271641. DOI: 10.4161/spmg.1.4.18326. View

14.

Tilley A, Walters M, Shaykhiev R, Crystal R . Cilia dysfunction in lung disease. Annu Rev Physiol. 2014; 77:379-406. PMC: 4465242. DOI: 10.1146/annurev-physiol-021014-071931. View

15.

Fliegauf M, Kahle A, Haffner K, Zieger B . Distinct localization of septin proteins to ciliary sub-compartments in airway epithelial cells. Biol Chem. 2013; 395(2):151-6. DOI: 10.1515/hsz-2013-0252. View

16.

Abbey M, Hakim C, Anand R, Lafera J, Schambach A, Kispert A . GTPase domain driven dimerization of SEPT7 is dispensable for the critical role of septins in fibroblast cytokinesis. Sci Rep. 2016; 6:20007. PMC: 4730212. DOI: 10.1038/srep20007. View

17.

Avasthi P, Marshall W . Stages of ciliogenesis and regulation of ciliary length. Differentiation. 2011; 83(2):S30-42. PMC: 3269565. DOI: 10.1016/j.diff.2011.11.015. View

18.

Xie Y, Vessey J, Konecna A, Dahm R, Macchi P, Kiebler M . The GTP-binding protein Septin 7 is critical for dendrite branching and dendritic-spine morphology. Curr Biol. 2007; 17(20):1746-51. DOI: 10.1016/j.cub.2007.08.042. View

19.

Sitz J, Baumgartel K, Hammerle B, Papadopoulos C, Hekerman P, Tejedor F . The Down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4. Neuroscience. 2008; 157(3):596-605. DOI: 10.1016/j.neuroscience.2008.09.034. View

20.

Kremer B, Adang L, Macara I . Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell. 2007; 130(5):837-50. PMC: 2085444. DOI: 10.1016/j.cell.2007.06.053. View