The Rap1-cofilin-1 pathway coordinates actin reorganization and MTOC polarization at the B cell immune synapse.
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.
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Jia C
JC
Wang
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Jeff Y-J
JY
Lee
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Sonja
S
Christian
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
May
M
Dang-Lawson
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Caitlin
C
Pritchard
Department of Microbiology & Immunology and the Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Spencer A
SA
Freeman
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.
Michael R
0000-0003-1222-3191
MR
Gold
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D051338:Cofilin 1 / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism; D005260:Female; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
D000199:Actins; D051338:Cofilin 1; C101203:IQ motif containing GTPase activating protein 1; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011947:Receptors, Antigen, B-Cell; D020703:ras GTPase-Activating Proteins; C076744:cytoplasmic linker protein 170; D004398:Dyneins; C000620839:Rap1 protein, mouse; D020827:rap1 GTP-Binding Proteins
B cell; Cofilin; Immune synapse; Microtubule-organizing center; Rap1