Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/88474
Title: 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
Authors: Ong, Seow Theng
Chalasani, Madhavi Latha Somaraju
Turabe Fazil, Mobashar Hussain Urf
Prasannan, Praseetha
Kizhakeyil, Atish
Wright, Graham D.
Kelleher, Dermot
Verma, Navin Kumar
Keywords: T-cell Migration
AKAP450
Issue Date: 2018
Source: Ong, 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-.
Series/Report no.: Frontiers in Immunology
Abstract: 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 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.
URI: https://hdl.handle.net/10356/88474
http://hdl.handle.net/10220/44628
DOI: 10.3389/fimmu.2018.00397
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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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