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J Cell Sci. 2017 Mar 15;130(6):1094-1109. doi: 10.1242/jcs.191858. Epub 2017 Feb 6.

The Rap1-cofilin-1 pathway coordinates actin reorganization and MTOC polarization at the B cell immune synapse.

Author information

1
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
2
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 mgold@mail.ubc.ca.

Abstract

B cells that bind antigens displayed on antigen-presenting cells (APCs) form an immune synapse, a polarized cellular structure that optimizes the dual functions of the B cell receptor (BCR), signal transduction and antigen internalization. Immune synapse formation involves polarization of the microtubule-organizing center (MTOC) towards the APC. We now show that BCR-induced MTOC polarization requires the Rap1 GTPase (which has two isoforms, Rap1a and Rap1b), an evolutionarily conserved regulator of cell polarity, as well as cofilin-1, an actin-severing protein that is regulated by Rap1. MTOC reorientation towards the antigen contact site correlated strongly with cofilin-1-dependent actin reorganization and cell spreading. We also show that BCR-induced MTOC polarization requires the dynein motor protein as well as IQGAP1, a scaffolding protein that can link the actin and microtubule cytoskeletons. At the periphery of the immune synapse, IQGAP1 associates closely with F-actin structures and with the microtubule plus-end-binding protein CLIP-170 (also known as CLIP1). Moreover, the accumulation of IQGAP1 at the antigen contact site depends on F-actin reorganization that is controlled by Rap1 and cofilin-1. Thus the Rap1-cofilin-1 pathway coordinates actin and microtubule organization at the immune synapse.

KEYWORDS:

B cell; Cofilin; Immune synapse; Microtubule-organizing center; Rap1

PMID:
28167682
DOI:
10.1242/jcs.191858
[Indexed for MEDLINE]
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