Developmental Neuroscience

Hamada N.a· Iwamoto I.a· Noda M.a· Nishikawa M.a· Nagataa K.b

Author affiliations

aDepartment of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai, Japan
bDepartment of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan

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Article / Publication Details

First-Page Preview

Received: July 04, 2022
Accepted: August 30, 2022
Published online: September 06, 2022

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE

Abstract

Polo-like kinase 4 (Plk4) is a ser/thr kinase, which plays a central role in centriole duplication during the cell cycle. PLK4 gene abnormalities are responsible for autosomal recessive chorioretinopathy-microcephaly syndrome and Seckel syndrome. In this study, we performed expression analyses of Plk4 by focusing on mouse brain development. Western blotting analyses revealed that Plk4 with a molecular mass of ∼100 kDa was broadly expressed in adult mouse tissues with specific subcellular distribution. As to the central nervous system, Plk4 was expressed throughout the developmental process with drastic increase after P15, suggesting an essential role of Plk4 in differentiated neurons. In immunohistochemical analyses with mouse brain at embryonic day 14, Plk4 was detected dominantly at the cell-cell contact sites of neuronal progenitors in the ventricular zone. Plk4 was then diffusely distributed in the cell body of cortical neurons at P7, while it was enriched in the neuropil as well as soma of excitatory neurons in the cerebral cortex and hippocampus and Purkinje cells in the cerebellum at P30. Notably, biochemical fractionation analysis found an enrichment of Plk4 in the postsynaptic density fraction. Then, immunofluorescent analyses showed partial co-localization of Plk4 with excitatory synaptic markers, PSD95 and synaptophysin, in differentiated primary cultured hippocampal neurons. These results suggest that Plk4 takes part in the regulation of synaptic function in differentiated neurons.

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References Varadarajan R, Rusan NM. Bridging centrioles and PCM in proper space and time. Essays in Biochemistry. 2018 Nov;62(6):793–801. Nigg EA, Raff JW. Centrioles, centrosomes, and cilia in health and disease. Cell. 2009 Nov;139(4):663–78. Fırat-Karalar EN, Stearns T. The centriole duplication cycle. Philos Trans R Soc Lond B Biol Sci. 2014 Sep;369(1650):20130460. Hamada N, Fujita Y, Tanaka A, Naoi M, Nozawa Y, Ono Y, et al. Metabolites of sesamin, a major lignan in sesame seeds, induce neuronal differentiation in PC12 cells through activation of ERK1/2 signaling pathway. J Neural Transm. 2009 Jun;116(7):841–52. Hamada N, Iwamoto I, Nishikawa M, Nagata K-I. Expression analyses of mediator complex subunit 13-like: a responsible gene for neurodevelopmental disorders during mouse brain development. Dev Neurosci. 2021;43(1):43–52. Hamada N, Iwamoto I, Kawamura N, Nagata K-I. Heterotrimeric G-protein, Gi1, is involved in the regulation of proliferation, neuronal migration, and dendrite morphology during cortical development in vivo. J Neurochem. 2021;157(4):1167–81. Ito H, Mizuno M, Noguchi K, Morishita R, Iwamoto I, Hara A, et al. Expression analyses of Phactr1 (phosphatase and actin regulator 1) during mouse brain development. Neurosci Res. 2018;128:50–7. Hamada N, Noda M, Ito H, Iwamoto I, Nagata K-I. Expression analyses of Cep152, a responsible gene product for autosomal recessive primary microcephaly, during mouse brain development. Dev Neurosci. 2022 Mar;44(3):162–70. Liao Z, Zhang H, Fan P, Huang Q, Dong K, Qi Y, et al. High PLK4 expression promotes tumor progression and induces epithelial-mesenchymal transition by regulating the Wnt/β-catenin signaling pathway in colorectal cancer. Int J Oncol. 2019;54(2):479–90. Fan G, Sun L, Shan P, Zhang X, Huan J, Zhang X, et al. Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nat Commun. 2015;6:8450–13. Zheng Y, Liu Y, Wang L, Xu H, Lu Z, Xuan Y, et al. MicroRNA-126 suppresses the proliferation and migration of endothelial cells in experimental diabetic retinopathy by targeting polo-like kinase 4. Int J Mol Med. 2021;47(1):151–60. Tian X, Zhou D, Chen L, Tian Y, Zhong B, Cao Y, et al. Polo-like kinase 4 mediates epithelial–mesenchymal transition in neuroblastoma via PI3K/Akt signaling pathway. Cell Death Dis. 2018 Jan;54:1–14. Shinmura K, Kato H, Kawanishi Y, Yoshimura K, Tsuchiya K, Takahara Y, et al. POLQ overexpression is associated with an increased somatic mutation load and PLK4 overexpression in lung adenocarcinoma. Cancers. 2019;11(5):722. Yang Z, Sun H, Ma W, Wu K, Peng G, Ou T, et al. Down regulation of Polo like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signaling pathway in bladder cancer. Febs Open Bio. 2021;11(9):2631–46. Lu Y, Zhou X, Liu Z, Wang W, Li F, Fu W. Characteristic analysis of featured genes associated with stemness indices in colorectal cancer. Frontiers Mol Biosci. 2020;7:563922. Harris RM, Weiss J, Jameson JL. Male hypogonadism and germ cell loss caused by a mutation in Polo-like kinase 4. Endocrinology. 2011;152(10):3975–85. David A, Amartely H, Rabinowicz N, Shamir M, Friedler A, Izraeli S. Molecular basis of the STIL coiled coil oligomerization explains its requirement for de-novo formation of centrosomes in mammalian cells. Sci Rep. 2016;6(1):24296. Nakagawa T, Araki T, Nakagawa M, Hirao A, Unno M, Nakayama K. S6 Kinase- and β-TrCP2-dependent degradation of p19Arf is required for cell proliferation. Mol Cell Biol. 2015;35(20):3517–27. Han Y, Chen L, Liu J, Chen J, Wang C, Guo Y, et al. A class I HDAC inhibitor rescues synaptic damage and neuron loss in APP-transfected cells and APP/PS1 mice through the GRIP1/AMPA pathway. Molecules. 2022;27(13):4160. Naisbitt S, Kim E, Weinberg RJ, Rao A, Yang FC, Craig AM, et al. Characterization of guanylate kinase-associated protein, a postsynaptic density protein at excitatory synapses that interacts directly with postsynaptic density-95/synapse-associated protein 90. J Neurosci Official J Soc Neurosci. 1997;17(15):5687–96. Ito H, Atsuzawa K, Sudo K, Di Stefano P, Iwamoto I, Morishita R, et al. Characterization of a multidomain adaptor protein, p140Cap, as part of a pre synaptic complex. J Neurochem. 2008;107(1):61–72. Noda M, Ito H, Nagata K-I. Physiological significance of WDR45, a responsible gene for β-propeller protein associated neurodegeneration (BPAN), in brain development. Sci Rep. 2021 Nov;11:22568–14. Shaheen R, Al Tala S, Almoisheer A, Alkuraya FS. Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. J Med Genet. 2014;51(12):814–6. Martin CA, Ahmad I, Klingseisen A, Hussain MS, Bicknell LS, Leitch A, et al. Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet. 2014 Oct;46(12):1283–92. Tsutsumi M, Yokoi S, Miya F, Miyata M, Kato M, Okamoto N, et al. Novel compound heterozygous variants in PLK4 identified in a patient with autosomal recessive microcephaly and chorioretinopathy. Eur J Hum Genet. 2016 Sep;24(12):1702–6. de Cárcer G, Escobar B, Higuero AM, García L, Ansón A, Pérez G, et al. Plk5, a polo box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression. Mol Cell Biol. 2011;31(6):1225–39. Kim TS, Park JE, Shukla A, Choi S, Murugan RN, Lee JH, et al. Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152. Proc National Acad Sci. 2013;110(50):E4849–57. Lee KS, Grenfell TZ, Yarm FR, Erikson RL. Mutation of the polo-box disrupts localization and mitotic functions of the mammalian polo kinase Plk. Proc National Acad Sci. 1998;95(16):9301–6. Song S, Grenfell TZ, Garfield S, Erikson RL, Lee KS. Essential function of the polo box of Cdc5 in subcellular localization and induction of cytokinetic structures. Mol Cell Biol. 2000;20(1):286–98. Article / Publication Details

First-Page Preview

Received: July 04, 2022
Accepted: August 30, 2022
Published online: September 06, 2022

Number of Print Pages: 8
Number of Figures: 3
Number of Tables: 0

ISSN: 0378-5866 (Print)
eISSN: 1421-9859 (Online)

For additional information: https://www.karger.com/DNE

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