The role of the gap junction protein connexin43 in B lymphocyte motility and migration.
The gap junction family of proteins is widely expressed in mammalian cells and form intercellular channels between adjacent cells, as well as hemichannels, for transport of molecules between the cell and the surrounding environment. In addition, gap junction proteins have recently been implicated as important for the regulation of cell adhesion and migration in a variety of cell types. The gap junction protein connexin43 (Cx43) regulates B lymphocyte adhesion, BCR- and LFA-1-mediated activation of the GTPase Rap1, and cytoskeletal rearrangements resulting in changes to cell shape and membrane spreading. We demonstrate here that the actin cytoskeleton is important for the distribution of Cx43 in the B cell plasma membrane and for other cell processes involving the cytoskeleton. Using shRNA knockdown of Cx43 in B lymphoma cells we show that Cx43 is also necessary for chemokine-mediated Rap 1 activation, motility, CXCL12-directed migration, and movement across an endothelial cell monolayer. These results demonstrate that in addition to its role in B cell spreading, Cx43 is an important regulator of B-cell motility and migration, processes essential for normal B-cell development and immune responses.
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Steven
S
Machtaler
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Kate
K
Choi
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
May
M
Dang-Lawson
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Letitia
L
Falk
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Farnaz
F
Pournia
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Neuroscience Research Group, Life Sciences Institute, Dept of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Christian C
CC
Naus
CELL and I(3) Research Groups, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: matsuchi@zoology.ubc.ca.
Linda
L
Matsuuchi
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D051381:Rats; D057705:Transendothelial and Transepithelial Migration; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
D054377:Chemokine CXCL12; D018031:Connexin 43; D020827:rap1 GTP-Binding Proteins
B-lymphocyte; Cx43; Cytoskeleton