Centrosome- 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 a-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.
CITATION STYLE
Ong, S. T., Chalasani, M. L. S., Fazil, M. H. U. T., Prasannan, P., Kizhakeyil, A., Wright, G. D., … Verma, N. K. (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(MAR). https://doi.org/10.3389/fimmu.2018.00397
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