Protein kinase CK2 (CK2) is a highly conserved and ubiquitous kinase is involved in crucial biological processes, including proliferation, migration, and differentiation. CK2 holoenzyme is a tetramer composed by two catalytically active (α/α’) and two regulatory (β) subunits and exerts its function on a broad range of targets. In the brain, it regulates different steps of neurodevelopment, such as neural differentiation, neuritogenesis, and synaptic plasticity. Interestingly, CK2 mutations have been recently linked to neurodevelopmental disorders; however, the functional requirements of the individual CK2 subunits in neurodevelopment have not been yet investigated. Here, we disclose the role of CK2 on the migration and adhesion properties of GN11 cells, an established model of mouse immortalized neurons, by different in vitro experimental approaches. Specifically, the cellular requirement of this kinase has been assessed pharmacologically and genetically by exploiting CK2 inhibitors and by generating subunit-specific CK2 knockout GN11 cells (with a CRISPR/Cas9-based approach). We show that CK2α’ subunit has a primary role in increasing cell adhesion and reducing migration properties of GN11 cells by activating the Akt-GSK3β axis, whereas CK2α subunit is dispensable. Further, the knockout of the CK2β regulatory subunits counteracts cell migration, inducing dramatic alterations in the cytoskeleton not observed in CK2α’ knockout cells. Collectively taken, our data support the view that the individual subunits of CK2 play different roles in cell migration and adhesion properties of GN11 cells, supporting independent roles of the different subunits in these processes.
Protein kinase CK2 subunits differentially perturb the adhesion and migration of GN11 cells: A model of immature migrating neurons / A. Lettieri, C. Borgo, L. Zanieri, C. D'amore, R. Oleari, A. Paganoni, L.A. Pinna, A. Cariboni, M. Salvi. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 20:23(2019 Dec 01).
|Titolo:||Protein kinase CK2 subunits differentially perturb the adhesion and migration of GN11 cells: A model of immature migrating neurons|
LETTIERI, ANTONELLA (Primo)
BORGO, FRANCESCA CLAUDIA (Secondo)
CARIBONI, ANNA MARIA (Penultimo) (Corresponding)
|Parole Chiave:||Cell adhesion; CK2 kinase; Microfilaments; Neuronal migration; Signaling pathways|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||1-dic-2019|
|Data ahead of print / Data di stampa:||nov-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/ijms20235951|
|Appare nelle tipologie:||01 - Articolo su periodico|