A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation.
T cell shape is dictated by the selective recruitment of molecules to different regions of the cell (polarity) and is integral to every aspect of T cell function, from migration to cytotoxicity. This study describes a mechanism for the regulation of T cell polarity. We show that T cells contain a network of asymmetrically distributed proteins with the capacity to dictate the subcellular localization of both cell surface receptors and morphological determinants in T cells. Proteins from the Scribble, Crumbs3, and Par3 complexes, previously shown to regulate epithelial polarity, were polarized in T cells containing either uropods or immunological synapses. Reduction in Scribble expression prevented the polarization of cell surface receptors and prevented morphological changes associated with uropod formation, migration, and antigen presentation. By dynamically coordinating molecular distribution throughout the T cell, this network provides a mechanism by which T cell function and polarity are linked.
Ludford-Menting
Mandy J
MJ
Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
Oliaro
Jane
J
Sacirbegovic
Faruk
F
Cheah
Eric T-Y
ET
Pedersen
Natalie
N
Thomas
Suzanne J
SJ
Pasam
Anupama
A
Iazzolino
Rosa
R
Dow
Lukas E
LE
Waterhouse
Nigel J
NJ
Murphy
Amanda
A
Ellis
Sarah
S
Smyth
Mark J
MJ
Kershaw
Michael H
MH
Darcy
Phillip K
PK
Humbert
Patrick O
PO
Russell
Sarah M
SM
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology*; D048430:Cell Shape / Q000276:immunology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D008565:Membrane Proteins