Ciliary Transition Zone Activation of Phosphorylated Tctex-1 Controls Ciliary Resorption, S-phase Entry and Fate of Neural Progenitors

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2011 Mar 12

PMID 21394082

Citations 131

Authors

Aiqun Li

Masaki Saito

Jen-Zen Chuang

Yun-Yu Tseng

Carlos Dedesma

Kazuhito Tomizawa

Taku Kaitsuka

Ching-Hwa Sung

Affiliations

Soon will be listed here.

Abstract

Primary cilia are displayed during the G(0)/G(1) phase of many cell types. Cilia are resorbed as cells prepare to re-enter the cell cycle, but the causal and molecular link between these two cellular events remains unclear. We show that Tctex-1 phosphorylated at Thr 94 is recruited to ciliary transition zones before S-phase entry and has a pivotal role in both ciliary disassembly and cell cycle progression. However, the role of Tctex-1 in S-phase entry is dispensable in non-ciliated cells. Exogenously adding a phospho-mimic Tctex-1(T94E) mutant accelerates cilium disassembly and S-phase entry. These results support a model in which the cilia act as a brake to prevent cell cycle progression. Mechanistic studies show the involvement of actin dynamics in Tctex-1-regulated cilium resorption. Tctex-1 phosphorylated at Thr 94 is also selectively enriched at the ciliary transition zones of cortical neural progenitors, and has a key role in controlling G(1) length, cell cycle entry and fate determination of these cells during corticogenesis.

Citing Articles

Loss of Downregulates Expression, Causing Cortical Development Disorders and Congenital Hydrocephalus.

Sakamoto K, Miyajima M, Nakajima M, Ogino I, Horikoshi K, Miyahara R Cells. 2024; 13(22).

PMID: 39594631 PMC: 11593149. DOI: 10.3390/cells13221882.

TAOK2 Drives Opposing Cilia Length Deficits in 16p11.2 Deletion and Duplication Carriers.

Ferreccio A, Byeon S, Cornell M, Oses-Prieto J, Deshpande A, Weiss L bioRxiv. 2024; .

PMID: 39416068 PMC: 11482803. DOI: 10.1101/2024.10.07.617069.

Actin cytoskeletal regulation of ciliogenesis in development and disease.

Hufft-Martinez B, Wang H, Saadi I, Tran P Dev Dyn. 2024; 253(12):1076-1093.

PMID: 38958410 PMC: 11611694. DOI: 10.1002/dvdy.724.

Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone .

Xu S, Zhang X, Li Z, Liu C, Liu Q, Chai H Front Cell Neurosci. 2024; 18:1391556.

PMID: 38841203 PMC: 11151745. DOI: 10.3389/fncel.2024.1391556.

GDF15 controls primary cilia morphology and function thereby affecting progenitor proliferation.

Baur K, San S, Holzl-Wenig G, Mandl C, Hellwig A, Ciccolini F Life Sci Alliance. 2024; 7(7).

PMID: 38719753 PMC: 11077589. DOI: 10.26508/lsa.202302384.

References

Pan J, Snell W . The primary cilium: keeper of the key to cell division. Cell. 2007; 129(7):1255-7. DOI: 10.1016/j.cell.2007.06.018. View

Follit J, Tuft R, Fogarty K, Pazour G . The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly. Mol Biol Cell. 2006; 17(9):3781-92. PMC: 1593158. DOI: 10.1091/mbc.e06-02-0133. View

Matsushita M, Tomizawa K, Moriwaki A, Li S, Terada H, Matsui H . A high-efficiency protein transduction system demonstrating the role of PKA in long-lasting long-term potentiation. J Neurosci. 2001; 21(16):6000-7. PMC: 6763134. View

Thomas M, Lu J, Ge Q, Zhang C, Chen J, Klibanov A . Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung. Proc Natl Acad Sci U S A. 2005; 102(16):5679-84. PMC: 556302. DOI: 10.1073/pnas.0502067102. View

Tai A, Chuang J, Sung C . Localization of Tctex-1, a cytoplasmic dynein light chain, to the Golgi apparatus and evidence for dynein complex heterogeneity. J Biol Chem. 1998; 273(31):19639-49. DOI: 10.1074/jbc.273.31.19639. View

Shu T, Ayala R, Nguyen M, Xie Z, Gleeson J, Tsai L . Ndel1 operates in a common pathway with LIS1 and cytoplasmic dynein to regulate cortical neuronal positioning. Neuron. 2004; 44(2):263-77. DOI: 10.1016/j.neuron.2004.09.030. View

Tabata H, Nakajima K . Efficient in utero gene transfer system to the developing mouse brain using electroporation: visualization of neuronal migration in the developing cortex. Neuroscience. 2001; 103(4):865-72. DOI: 10.1016/s0306-4522(01)00016-1. View

Murcia N, Richards W, Yoder B, Mucenski M, Dunlap J, Woychik R . The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left-right axis determination. Development. 2000; 127(11):2347-55. DOI: 10.1242/dev.127.11.2347. View

Xia X, Zhou H, Ding H, Affar E, Shi Y, Xu Z . An enhanced U6 promoter for synthesis of short hairpin RNA. Nucleic Acids Res. 2003; 31(17):e100. PMC: 212820. DOI: 10.1093/nar/gng098. View

10.

Jia J, Kolterud A, Zeng H, Hoover A, Teglund S, Toftgard R . Suppressor of Fused inhibits mammalian Hedgehog signaling in the absence of cilia. Dev Biol. 2009; 330(2):452-60. PMC: 2687323. DOI: 10.1016/j.ydbio.2009.04.009. View

11.

Kim J, Lee J, Heynen-Genel S, Suyama E, Ono K, Lee K . Functional genomic screen for modulators of ciliogenesis and cilium length. Nature. 2010; 464(7291):1048-51. PMC: 2929961. DOI: 10.1038/nature08895. View

12.

Chenn A, Walsh C . Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science. 2002; 297(5580):365-9. DOI: 10.1126/science.1074192. View

13.

Pfister K, Fisher E, Gibbons I, Hays T, Holzbaur E, McIntosh J . Cytoplasmic dynein nomenclature. J Cell Biol. 2005; 171(3):411-3. PMC: 2171247. DOI: 10.1083/jcb.200508078. View

14.

Calegari F, Huttner W . An inhibition of cyclin-dependent kinases that lengthens, but does not arrest, neuroepithelial cell cycle induces premature neurogenesis. J Cell Sci. 2003; 116(Pt 24):4947-55. DOI: 10.1242/jcs.00825. View

15.

Mahjoub M, Rasi M, Quarmby L . A NIMA-related kinase, Fa2p, localizes to a novel site in the proximal cilia of Chlamydomonas and mouse kidney cells. Mol Biol Cell. 2004; 15(11):5172-86. PMC: 524795. DOI: 10.1091/mbc.e04-07-0571. View

16.

Gotz M, Huttner W . The cell biology of neurogenesis. Nat Rev Mol Cell Biol. 2005; 6(10):777-88. DOI: 10.1038/nrm1739. View

17.

Higginbotham H, Gleeson J . The centrosome in neuronal development. Trends Neurosci. 2007; 30(6):276-83. DOI: 10.1016/j.tins.2007.04.001. View

18.

Schneider L, Clement C, Teilmann S, Pazour G, Hoffmann E, Satir P . PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr Biol. 2005; 15(20):1861-6. DOI: 10.1016/j.cub.2005.09.012. View

19.

Mittnacht S . Control of pRB phosphorylation. Curr Opin Genet Dev. 1998; 8(1):21-7. DOI: 10.1016/s0959-437x(98)80057-9. View

20.

Dedesma C, Chuang J, Alfinito P, Sung C . Dynein light chain Tctex-1 identifies neural progenitors in adult brain. J Comp Neurol. 2006; 496(6):773-86. DOI: 10.1002/cne.20958. View