title: A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation.
abstract: 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.
authors.affiliation: Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: Ludford-Menting
authors.forename: Jane
authors.initials: J
authors.lastname: Oliaro
authors.forename: Faruk
authors.initials: F
authors.lastname: Sacirbegovic
authors.forename: Eric T-Y
authors.initials: ET
authors.lastname: Cheah
authors.forename: Natalie
authors.initials: N
authors.lastname: Pedersen
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: Anupama
authors.initials: A
authors.lastname: Pasam
authors.forename: Rosa
authors.initials: R
authors.lastname: Iazzolino
authors.forename: Lukas E
authors.initials: LE
authors.lastname: Dow
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Waterhouse
authors.forename: Amanda
authors.initials: A
authors.lastname: Murphy
authors.forename: Sarah
authors.initials: S
authors.lastname: Ellis
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Michael H
authors.initials: MH
authors.lastname: Kershaw
authors.forename: Phillip K
authors.initials: PK
authors.lastname: Darcy
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Humbert
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Russell
mesh_terms: 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
chemical_list: D008565:Membrane Proteins