title: Activation-induced endocytosis of the raft-associated transmembrane adaptor protein LAB/NTAL in B lymphocytes: evidence for a role in internalization of the B cell receptor.
abstract: Linker for activation of B cell (LAB)/non-T cell activation linker (NTAL) and phosphoprotein associated with glycophospholipid-enriched membrane microdomain (PAG)/Csk-binding protein (Cbp) are raft-associated transmembrane adaptor proteins with distinct functions in immediate/early phases of receptor signaling pathways. Heterogeneous rafts are thought to compartmentalize membrane-associated signaling events. In order to investigate the subcellular localization of LAB/NTAL and PAG/Cbp, they were expressed as fluorescent chimeric fusion proteins in a human B cell line and their distribution was examined, along with the corresponding endogenous proteins, before and after B cell receptor (BCR) stimulation. Both adaptors were distributed predominantly at the plasma membrane in resting cells and co-clustered with other raft-associated proteins; however, they distributed differently in buoyant membranes isolated by either detergent resistance or non-detergent methods, indicating that they might localize to distinct rafts. After activation, LAB/NTAL was internalized and co-localized with the BCR while PAG/Cbp remained on the cell surface. BCR internalization was reduced in LAB/NTAL-deficient murine B cells, suggesting a regulatory role for LAB/NTAL in activation-induced internalization of the BCR. The cytoplasmic domain of LAB/NTAL, and not the transmembrane/juxtamembrane region, was found to be essential for its internalization.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Health Sciences Center, 3330 Hospital Drive North West, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Cathlin M
authors.initials: CM
authors.lastname: Mutch
authors.forename: Ratna
authors.initials: R
authors.lastname: Sanyal
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Unruh
authors.forename: Lana
authors.initials: L
authors.lastname: Grigoriou
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
authors.forename: Julie P
authors.initials: JP
authors.lastname: Deans
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D002478:Cells, Cultured; D004705:Endocytosis; D049452:Green Fluorescent Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C471359:LAB protein, mouse; D011947:Receptors, Antigen, B-Cell; D049452:Green Fluorescent Proteins