Hostname: page-component-848d4c4894-hfldf Total loading time: 0 Render date: 2024-05-08T14:19:51.962Z Has data issue: false hasContentIssue false
  • English
  • Français

CD81 Promotes a Migratory Phenotype in Neuronal-Like Cells

Published online by Cambridge University Press:  04 February 2019

Soraia A. Martins ,
Patrícia D. Correia ,
Roberto A. Dias ,
Odete A.B. da Cruz e Silva  and
Sandra I. Vieira Open the ORCID record for Sandra I. Vieira [Opens in a new window]
Soraia A. Martins
Affiliation:
Department of Medical Sciences, Cell Differentiation and Regeneration Laboratory, Institute of Biomedicine (iBiMED), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal Department of Medical Sciences, Neurosciences and Signalling Laboratory, Institute of Biomedicine (iBiMED), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
Patrícia D. Correia
Affiliation:
Department of Medical Sciences, Cell Differentiation and Regeneration Laboratory, Institute of Biomedicine (iBiMED), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
Roberto A. Dias
Affiliation:
Department of Medical Sciences, Cell Differentiation and Regeneration Laboratory, Institute of Biomedicine (iBiMED), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal Department of Medical Sciences, Neurosciences and Signalling Laboratory, Institute of Biomedicine (iBiMED), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal
Odete A.B. da Cruz e Silva
Affiliation:
Department of Medical Sciences, Neurosciences and Signalling Laboratory, Institute of Biomedicine (iBiMED), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal The Discovery CTR, University of Aveiro Campus, 3810-193 Aveiro, Portugal
Sandra I. Vieira*
Affiliation:
Department of Medical Sciences, Cell Differentiation and Regeneration Laboratory, Institute of Biomedicine (iBiMED), Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal The Discovery CTR, University of Aveiro Campus, 3810-193 Aveiro, Portugal
*
*Author for correspondence: Sandra I. Vieira, E-mail: sivieira@ua.pt
Get access

Abstract

Tetraspanins, such as CD81, can form lateral associations with each other and with other transmembrane proteins. These interactions may underlie CD81 functions in multiple cellular processes, such as adhesion, morphology, migration, and differentiation. Since CD81's role in neuronal cells’ migration has not been established, we here evaluated effects of CD81 on the migratory phenotype of SH-SY5Y neuroblastoma cells. CD81 was found enriched at SH-SY5Y cell's membrane, co-localizing with its interactor filamentous-actin (F-actin) in migratory relevant structures of the leading edge (filopodia, stress fibers, and adhesion sites). CD81 overexpression increased the number of cells with a migratory phenotype, in a potentially phosphatidylinositol 3 kinase (PI3K)–Ak strain transforming (AKT) mediated manner. Indeed, CD81 also co-localized with AKT, a CD81-interactor and actin remodeling agent, at the inner leaflet of the plasma membrane. Pharmacologic inhibition of PI3K, the canonical AKT activator, led both to a decrease in the acquisition of a migratory phenotype and to a redistribution of intracellular CD81 and F-actin into cytoplasmic agglomerates. These findings suggest that in neuronal-like cells CD81 bridges active AKT and actin, promoting the actin remodeling that leads to a motile cell morphology. Further studies on this CD81-mediated mechanism will improve our knowledge on important physiological and pathological processes such as cell migration and differentiation, and tumor metastasis.

Keywords

actin remodelingCD81 tetraspaninneuronal migrationPI3K–AKT signalingSH-SY5Y neuroblastoma cells
Type
Life Sciences
Information
Microscopy and Microanalysis , Volume 25 , Issue 1 , February 2019 , pp. 229 - 235
Copyright
Copyright © Microscopy Society of America 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

Current address: Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany.

‡

Equally contributing authors.

References

Andreu, Z and Yáñez-Mó, M (2014) Tetraspanins in extracellular vesicle formation and function. Front Immunol 5, 442.Google Scholar
Auer, S, Rinnerthaler, M, Bischof, J, Streubel, MK, Breitenbach-Koller, H, Geisberger, R, Aigner, E, Cadamuro, J, Richter, K, Sopjani, M, Haschke-Becher, E, Felder, TK and Breitenbach, MM (2017) The human NADPH oxidase, Nox4, regulates cytoskeletal organization in two cancer cell lines, HepG2 and SH-SY5Y. Front Oncol 7, 111.Google Scholar
Bari, R, Guo, Q, Xia, B, Zhang, YH, Geisert, EE, Levy, S, Zheng, JJ and Zhang, XA (2011) Tetraspanins regulate the protrusive activities of cell membrane. Biochem Biophys Res Commun 415(4), 619–626.Google Scholar
Boucheix, C and Rubinstein, E (2001) Tetraspanins. Cell Mol Life Sci: CMLS 58(9), 1189–205.Google Scholar
da Rocha, JF, da Cruz e Silva, OAB and Vieira, SI (2015) Analysis of the amyloid precursor protein role in neuritogenesis reveals a biphasic SH-SY5Y neuronal cell differentiation model. J Neurochem 134(2), 288–301.Google Scholar
Dijkstra, S, Geisert, EE JR, Gispen, WH, Bär, PR and Joosten, EA (2000) Up-regulation of CD81 (target of the antiproliferative antibody; TAPA) by reactive microglia and astrocytes after spinal cord injury in the rat. J Comp Neurol 428(2), 266–77.Google Scholar
Geisert, EE, Williams, RW, Geisert, GR, Fan, L, Asbury, AM, Maecker, HT, Deng, J and Levy, S (2002) Increased brain size and glial cell number in CD81-null mice. J Comp Neurol 453(1), 22–32.Google Scholar
Gordon, J, Amini, S and White, MK (2013) General overview of neuronal cell culture. Methods Mol Biol (Clifton, N.J.), 1078, 1–8.Google Scholar
Hall, A (1998) Rho GTPases and the actin cytoskeleton. Science (New York, N.Y.), 279(5350), 509–14.Google Scholar
Hemler, ME (2005) Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 6(10), 801–11.Google Scholar
Jiang, X, Zhang, J and Huang, Y (2015) Tetraspanins in cell migration. Cell Adhes Migr 9(5), 406–415.Google Scholar
Kelić, S, Levy, S, Suarez, C and Weinstein, DE (2001) CD81 regulates neuron-induced astrocyte cell-cycle exit. Mol Cell Neurosci 17(3), 551–560.Google Scholar
Koh, SH and Lo, EH (2015) The role of the PI3K pathway in the regeneration of the damaged brain by neural stem cells after cerebral infarction. J Clin Neurol (Korea) 11, 297–304.Google Scholar
Kovalevich, J and Langford, D (2013) Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods Mol Biol (Clifton, N.J.), 1078, 9–21.Google Scholar
Levy, S, Todd, SC and Maecker, HT (1998) CD81 (TAPA-1): A molecule involved in signal transduction and cell adhesion in the immune system. Annu Rev Immunol 16, 89–109.Google Scholar
Marín, O, Valiente, M, Ge, X and Tsai, L-H (2010) Guiding neuronal cell migrations. Cold Spring Harbor Perspect Biol 2(2), a001834.Google Scholar
Perez-Hernandez, D, Gutiérrez-Vázquez, C, Jorge, I, López-Martín, S, Ursa, A, Sánchez-Madrid, F, Vázquez, J and Yáñez-Mó, M (2013) The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J Biol Chem 288(17), 11649–61.10.1074/jbc.M112.445304Google Scholar
Qian, Y, Corum, L, Meng, Q, Blenis, J, Zheng, JZ, Shi, X, Flynn, DC and Jiang, BH (2004) PI3K induced actin filament remodeling through Akt and p70S6K1: Implication of essential role in cell migration. Am J Physiol-Cell Physiol 286(1), C153–C163.Google Scholar
Qian, Y, Zhong, X, Flynn, DC, Zheng, JZ, Qiao, M, Wu, C, Dedhar, S, Shi, X and Jiang, BH (2005) ILK mediates actin filament rearrangements and cell migration and invasion through PI3K/Akt/Rac1 signaling. Oncogene 24(19), 3154–3165.Google Scholar
Shoham, T, Rajapaksa, R, Kuo, C-C, Haimovich, J and Levy, S (2006) Building of the tetraspanin web: Distinct structural domains of CD81 function in different cellular compartments. Mol Cell Biol 26(4), 1373–85.Google Scholar
Tejera, E, Rocha-Perugini, V, López-Martín, S, Pérez-Hernández, D, Bachir, AI, Horwitz, AR, Vázquez, J, Sánchez-Madrid, F and Yáñez-Mo, M (2013) CD81 regulates cell migration through its association with Rac GTPase. Mol Biol Cell 24(3), 261–73.10.1091/mbc.e12-09-0642Google Scholar
Xue, G, Hemmings, BA (2013) PKB/Akt-dependent regulation of cell motility. J Natl Cancer Inst 105(6), 393–404.Google Scholar
Yu, JSL and Cui, W (2016) Proliferation, survival and metabolism: The role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development 143(17), 3050–3060.Google Scholar