---
_id: '9379'
abstract:
- lang: eng
text: When B cells encounter membrane-bound antigens, the formation and coalescence
of B cell antigen receptor (BCR) microclusters amplifies BCR signaling. The ability
of B cells to probe the surface of antigen-presenting cells (APCs) and respond
to APC-bound antigens requires remodeling of the actin cytoskeleton. Initial BCR
signaling stimulates actin-related protein (Arp) 2/3 complex-dependent actin polymerization,
which drives B cell spreading as well as the centripetal movement and coalescence
of BCR microclusters at the B cell-APC synapse. Sustained actin polymerization
depends on concomitant actin filament depolymerization, which enables the recycling
of actin monomers and Arp2/3 complexes. Cofilin-mediated severing of actin filaments
is a rate-limiting step in the morphological changes that occur during immune
synapse formation. Hence, regulators of cofilin activity such as WD repeat-containing
protein 1 (Wdr1), LIM domain kinase (LIMK), and coactosin-like 1 (Cotl1) may also
be essential for actin-dependent processes in B cells. Wdr1 enhances cofilin-mediated
actin disassembly. Conversely, Cotl1 competes with cofilin for binding to actin
and LIMK phosphorylates cofilin and prevents it from binding to actin filaments.
We now show that Wdr1 and LIMK have distinct roles in BCR-induced assembly of
the peripheral actin structures that drive B cell spreading, and that cofilin,
Wdr1, and LIMK all contribute to the actin-dependent amplification of BCR signaling
at the immune synapse. Depleting Cotl1 had no effect on these processes. Thus,
the Wdr1-LIMK-cofilin axis is critical for BCR-induced actin remodeling and for
B cell responses to APC-bound antigens.
acknowledgement: We thank the UBC Life Sciences Institute Imaging Facility andthe
UBC Flow Cytometry Facility.
article_number: '649433'
article_processing_charge: No
article_type: original
author:
- first_name: Madison
full_name: Bolger-Munro, Madison
id: 516F03FA-93A3-11EA-A7C5-D6BE3DDC885E
last_name: Bolger-Munro
orcid: 0000-0002-8176-4824
- first_name: Kate
full_name: Choi, Kate
last_name: Choi
- first_name: Faith
full_name: Cheung, Faith
last_name: Cheung
- first_name: Yi Tian
full_name: Liu, Yi Tian
last_name: Liu
- first_name: May
full_name: Dang-Lawson, May
last_name: Dang-Lawson
- first_name: Nikola
full_name: Deretic, Nikola
last_name: Deretic
- first_name: Connor
full_name: Keane, Connor
last_name: Keane
- first_name: Michael R.
full_name: Gold, Michael R.
last_name: Gold
citation:
ama: Bolger-Munro M, Choi K, Cheung F, et al. The Wdr1-LIMK-Cofilin axis controls
B cell antigen receptor-induced actin remodeling and signaling at the immune synapse.
Frontiers in Cell and Developmental Biology. 2021;9. doi:10.3389/fcell.2021.649433
apa: Bolger-Munro, M., Choi, K., Cheung, F., Liu, Y. T., Dang-Lawson, M., Deretic,
N., … Gold, M. R. (2021). The Wdr1-LIMK-Cofilin axis controls B cell antigen receptor-induced
actin remodeling and signaling at the immune synapse. Frontiers in Cell and
Developmental Biology. Frontiers Media. https://doi.org/10.3389/fcell.2021.649433
chicago: Bolger-Munro, Madison, Kate Choi, Faith Cheung, Yi Tian Liu, May Dang-Lawson,
Nikola Deretic, Connor Keane, and Michael R. Gold. “The Wdr1-LIMK-Cofilin Axis
Controls B Cell Antigen Receptor-Induced Actin Remodeling and Signaling at the
Immune Synapse.” Frontiers in Cell and Developmental Biology. Frontiers
Media, 2021. https://doi.org/10.3389/fcell.2021.649433.
ieee: M. Bolger-Munro et al., “The Wdr1-LIMK-Cofilin axis controls B cell
antigen receptor-induced actin remodeling and signaling at the immune synapse,”
Frontiers in Cell and Developmental Biology, vol. 9. Frontiers Media, 2021.
ista: Bolger-Munro M, Choi K, Cheung F, Liu YT, Dang-Lawson M, Deretic N, Keane
C, Gold MR. 2021. The Wdr1-LIMK-Cofilin axis controls B cell antigen receptor-induced
actin remodeling and signaling at the immune synapse. Frontiers in Cell and Developmental
Biology. 9, 649433.
mla: Bolger-Munro, Madison, et al. “The Wdr1-LIMK-Cofilin Axis Controls B Cell Antigen
Receptor-Induced Actin Remodeling and Signaling at the Immune Synapse.” Frontiers
in Cell and Developmental Biology, vol. 9, 649433, Frontiers Media, 2021,
doi:10.3389/fcell.2021.649433.
short: M. Bolger-Munro, K. Choi, F. Cheung, Y.T. Liu, M. Dang-Lawson, N. Deretic,
C. Keane, M.R. Gold, Frontiers in Cell and Developmental Biology 9 (2021).
date_created: 2021-05-09T22:01:37Z
date_published: 2021-04-13T00:00:00Z
date_updated: 2023-10-18T08:19:49Z
day: '13'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.3389/fcell.2021.649433
external_id:
isi:
- '000644419500001'
pmid:
- '33928084'
file:
- access_level: open_access
checksum: 8c8a03575d2f7583f88dc3b658b0976b
content_type: application/pdf
creator: kschuh
date_created: 2021-05-11T15:09:23Z
date_updated: 2021-05-11T15:09:23Z
file_id: '9386'
file_name: 2021_Frontiers_Cell_Bolger-Munro.pdf
file_size: 4076024
relation: main_file
success: 1
file_date_updated: 2021-05-11T15:09:23Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
keyword:
- B cell
- actin
- immune synapse
- cell spreading
- cofilin
- WDR1 (AIP1)
- LIM domain kinase
- B cell receptor (BCR)
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Cell and Developmental Biology
publication_identifier:
eissn:
- 2296-634X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: The Wdr1-LIMK-Cofilin axis controls B cell antigen receptor-induced actin remodeling
and signaling at the immune synapse
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2021'
...