Abstract
Cytoskeletal dysregulation forms an important aspect of many neurodegenerative diseases such as Alzheimer’s disease. Cytoskeletal functions require the dynamic activity of the cytoskeletal proteins—actin, tubulin, and the associated proteins. One of such important phenomena is that of actin remodeling, which helps the cell to migrate, navigate, and interact with extracellular materials. Podosomes are complex actin-rich cytoskeletal structures, abundant in proteins that interact and degrade the extracellular matrix, enabling cells to displace and migrate. The formation of podosomes requires extensive actin networks and remodeling. Here we present a novel immunofluorescence-based approach to study actin remodeling in neurons through the medium of podosomes.
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References
Breijyeh Z, Karaman R (2020) Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules 25:5789. https://doi.org/10.3390/molecules25245789
Brion JP, Couck AM, Passareiro E, Flament-Durand J (1985) Neurofibrillary tangles of Alzheimer’s disease: an immunohistochemical study. J Submicrosc Cytol 17:89–96
Chen Y, Fu AKY, Ip NY (2019) Synaptic dysfunction in Alzheimer’s disease: mechanisms and therapeutic strategies. Pharmacol Ther 195:186–198. https://doi.org/10.1016/j.pharmthera.2018.11.006
Penzes P, VanLeeuwen J-E (2011) Impaired regulation of synaptic actin cytoskeleton in Alzheimer’s disease. Brain Res Rev 67:184–192. https://doi.org/10.1016/j.brainresrev.2011.01.003
Tracy TE, Gan L (2018) Tau-mediated synaptic and neuronal dysfunction in neurodegenerative disease. Curr Opin Neurobiol 51:134–138. https://doi.org/10.1016/j.conb.2018.04.027
Das R, Chinnathambi S (2020) Actin-mediated microglial chemotaxis via G-protein coupled purinergic receptor in Alzheimer’s disease. Neuroscience 448:325–336. https://doi.org/10.1016/j.neuroscience.2020.09.024
Das R, Chinnathambi S (2021) Microglial remodeling of actin network by tau oligomers, via G protein-coupled purinergic receptor, P2Y12R-driven chemotaxis. Traffic 22:153–170. https://doi.org/10.1111/tra.12784
Bamburg JR, Bloom GS (2009) Cytoskeletal pathologies of Alzheimer disease. Cell Motil Cytoskeleton 66:635–649. https://doi.org/10.1002/cm.20388
Muñoz-Lasso DC, Romá-Mateo C, Pallardó FV, Gonzalez-Cabo P (2020) Much more than a scaffold: cytoskeletal proteins in neurological disorders. Cell 9:358. https://doi.org/10.3390/cells9020358
Vickers JC, Kirkcaldie MT, Phipps A, King AE (2016) Alterations in neurofilaments and the transformation of the cytoskeleton in axons may provide insight into the aberrant neuronal changes of Alzheimer’s disease. Brain Res Bull 126:324–333. https://doi.org/10.1016/j.brainresbull.2016.07.012
Khan AN (2012) Involvement of actin pathology in Alzheimer’s disease. Cell Dev Biol 2012:02. https://doi.org/10.4172/2168-9296.1000e121
Gil-Henn H, Destaing O, Sims NA et al (2007) Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2−/− mice. J Cell Biol 178:1053–1064. https://doi.org/10.1083/jcb.200701148
Liu Z, Hao K-M, Wang H-Y, Qi W-X (2020) Histone deacetylase-6 modulates amyloid beta-induced cognitive dysfunction rats by regulating PTK2B. Neuroreport 31:754–761. https://doi.org/10.1097/WNR.0000000000001481
Palazzo AF, Joseph HL, Chen Y-J et al (2001) Cdc42, dynein, and dynactin regulate MTOC reorientation independent of rho-regulated microtubule stabilization. Curr Biol 11:1536–1541. https://doi.org/10.1016/S0960-9822(01)00475-4
Gomes ER, Jani S, Gundersen GG (2005) Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121:451–463. https://doi.org/10.1016/j.cell.2005.02.022
Weaver AM, Heuser JE, Karginov AV et al (2002) Interaction of Cortactin and N-WASp with Arp2/3 complex. Curr Biol 12:1270–1278. https://doi.org/10.1016/S0960-9822(02)01035-7
Nakanishi O, Suetsugu S, Yamazaki D, Takenawa T (2007) Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex. J Biochem 141:319–325. https://doi.org/10.1093/jb/mvm034
Korobova F, Svitkina T (2008) Arp2/3 complex is important for filopodia formation, growth cone motility, and neuritogenesis in neuronal cells. MBoC 19:1561–1574. https://doi.org/10.1091/mbc.e07-09-0964
San Miguel-Ruiz JE, Letourneau PC (2014) The role of Arp2/3 in growth cone actin dynamics and guidance is substrate dependent. J Neurosci 34:5895–5908. https://doi.org/10.1523/JNEUROSCI.0672-14.2014
Qureshi T, Chinnathambi S (1869) Histone deacetylase-6 modulates tau function in Alzheimer’s disease. Biochimica et Biophysica Acta (BBA) Mol Cell Res 2022:119275. https://doi.org/10.1016/j.bbamcr.2022.119275
Hurst IR, Zuo J, Jiang J, Holliday LS (2004) Actin-related protein 2/3 complex is required for actin ring formation. J Bone Miner Res 19:499–506. https://doi.org/10.1359/JBMR.0301238
Albiges-Rizo C, Destaing O, Fourcade B et al (2009) Actin machinery and mechanosensitivity in invadopodia, podosomes and focal adhesions. J Cell Sci 122:3037–3049. https://doi.org/10.1242/jcs.052704
Murphy DA, Courtneidge SA (2011) The “ins” and “outs” of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Biol 12:413–426. https://doi.org/10.1038/nrm3141
Linder S, Aepfelbacher M (2003) Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol 13:376–385. https://doi.org/10.1016/S0962-8924(03)00128-4
Vincent C, Siddiqui TA, Schlichter LC (2012) Podosomes in migrating microglia: components and matrix degradation. J Neuroinflammation 9:190. https://doi.org/10.1186/1742-2094-9-190
Courtneidge SA, Azucena EF, Pass I et al (2005) The SRC substrate Tks5, podosomes (invadopodia), and cancer cell invasion. Cold Spring Harb Symp Quant Biol 70:167–171. https://doi.org/10.1101/sqb.2005.70.014
Iizuka S, Abdullah C, Buschman MD et al (2016) The role of Tks adaptor proteins in invadopodia formation, growth and metastasis of melanoma. Oncotarget 7:78473–78486. https://doi.org/10.18632/oncotarget.12954
Pęziński M, Maliszewska-Olejniczak K, Daszczuk P et al (2021) Tks5 regulates synaptic podosome formation and stabilization of the postsynaptic machinery at the neuromuscular junction. Int J Mol Sci 22:12051. https://doi.org/10.3390/ijms222112051
Zambonin-Zallone A, Teti A, Grano M et al (1989) Immunocytochemical distribution of extracellular matrix receptors in human osteoclasts: a β3 integrin is colocalized with vinculin and talin in the podosomes of osteoclastoma giant cells. Exp Cell Res 182:645–652. https://doi.org/10.1016/0014-4827(89)90266-8
Acknowledgments
This project is supported by the in-house CSIR-National Chemical Laboratory grant MLP101726. The author is grateful to Chinnathambi’s lab members for their scientific suggestions on the manuscript. TQ acknowledges the Department of Science and Technology – Innovation in Science Pursuit for Inspired Research (DST-INSPIRE), the Government of India for her fellowship. The authors greatly acknowledge the Department of Neurochemistry, the National Institute of Mental Health and Neuro Sciences (NIMHANS), and the Institute of National Importance, Bangalore, for their internal support.
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Qureshi, T., Desale, S.E., Chidambaram, H., Chinnathambi, S. (2024). Understanding Actin Remodeling in Neuronal Cells Through Podosomes. In: Ray, S.K. (eds) Neuroprotection. Methods in Molecular Biology, vol 2761. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3662-6_18
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DOI: https://doi.org/10.1007/978-1-0716-3662-6_18
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