Original Research ARTICLE
CG-NAP serves as a docking platform for PKA signaling and microtubule nucleation in migrating T-cells
- 1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- 2Institute of Medical Biology (A*STAR), Singapore
- 3Faculty of Medicine, University of British Columbia, Canada
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 towards 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.
Keywords: T-cell migration, AKAP450, AKAP350, adaptor protein, Centrosomal proteins, Microtubules
Received: 07 Oct 2017;
Accepted: 13 Feb 2018.
Edited by:Francisco Sanchez-Madrid, Universidad Autonoma de Madrid, Spain
Reviewed by:Christoph Wülfing, University of Bristol, United Kingdom
Juan M. Serrador, Consejo Superior de Investigaciones Cientificas (CSIC), Spain
Andres Alcover, Institut Pasteur, France
Copyright: © 2018 Ong, Chalasani, Fazil, Prasannan, 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.
* Correspondence: Dr. Navin Kumar Verma, Nanyang Technological University, Lee Kong Chian School of Medicine, Experimental Medicine Building, 59 Nanyang Drive, Singapore, 636921, Singapore, email@example.com