dc.contributor.authorOng, Seow Theng
dc.contributor.authorChalasani, Madhavi Latha Somaraju
dc.contributor.authorTurabe Fazil, Mobashar Hussain Urf
dc.contributor.authorPrasannan, Praseetha
dc.contributor.authorKizhakeyil, Atish
dc.contributor.authorWright, Graham D.
dc.contributor.authorKelleher, Dermot
dc.contributor.authorVerma, Navin Kumar
dc.date.accessioned2018-03-28T04:26:43Z
dc.date.available2018-03-28T04:26:43Z
dc.date.issued2018
dc.identifier.citationOng, S. T., Chalasani, M. L. S., Turabe Fazil, M. H. U., Prasannan, P., Kizhakeyil, A., Wright, G. D., et al. (2018). Centrosome- and Golgi-Localized Protein Kinase N-Associated Protein Serves As a Docking Platform for Protein Kinase A Signaling and Microtubule Nucleation in Migrating T-Cells. Frontiers in Immunology, 9, 397-.en_US
dc.identifier.urihttp://hdl.handle.net/10220/44628
dc.description.abstractCentrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP), also known as AKAP450, is a cytosolic scaffolding protein involved in the targeted positioning of multiple signaling molecules, which are critical for cellular functioning. Here, we show that CG-NAP is predominantly expressed in human primary T-lymphocytes, localizes in close proximity (<0.2 μm) with centrosomal and Golgi structures and serves as a docking platform for Protein Kinase A (PKA). GapmeR-mediated knockdown of CG-NAP inhibits LFA-1-induced T-cell migration and impairs T-cell chemotaxis toward the chemokine SDF-1α. Depletion of CG-NAP dislocates PKARIIα, disrupts centrosomal and non-centrosomal microtubule nucleation, causes Golgi fragmentation, and impedes α-tubulin tyrosination and acetylation, which are important for microtubule dynamics and stability in migrating T-cells. Furthermore, we show that CG-NAP coordinates PKA-mediated phosphorylation of pericentrin and dynein in T-cells. Overall, our findings provide critical insights into the roles of CG-NAP in regulating cytoskeletal architecture and T-cell migration.en_US
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en_US
dc.format.extent16 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesFrontiers in Immunologyen_US
dc.rights© 2018 Ong, Chalasani, Fazil, Prasannan, Kizhakeyil, Wright, Kelleher and Verma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.subjectT-cell Migrationen_US
dc.subjectAKAP450en_US
dc.titleCentrosome- and Golgi-Localized Protein Kinase N-Associated Protein Serves As a Docking Platform for Protein Kinase A Signaling and Microtubule Nucleation in Migrating T-Cellsen_US
dc.typeJournal Article
dc.contributor.schoolLee Kong Chian School of Medicineen_US
dc.identifier.doihttp://dx.doi.org/10.3389/fimmu.2018.00397
dc.description.versionPublished versionen_US


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