The LFA-1-associated molecule PTA-1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large.
Clustering of the T cell integrin, LFA-1, at specialized regions of intercellular contact initiates integrin-mediated adhesion and downstream signaling, events that are necessary for a successful immunological response. But how clustering is achieved and sustained is not known. Here we establish that an LFA-1-associated molecule, PTA-1, is localized to membrane rafts and binds the carboxyl-terminal domain of isoforms of the actin-binding protein 4.1G. Protein 4.1 is known to associate with the membrane-associated guanylate kinase homologue, human discs large. We show that the carboxyl-terminal peptide of PTA-1 also can bind human discs large and that the presence or absence of this peptide greatly influences binding between PTA-1 and different isoforms of 4.1G. T cell stimulation with phorbol ester or PTA-1 cross-linking induces PTA-1 and 4.1G to associate tightly with the cytoskeleton, and the PTA-1 from such activated cells now can bind to the amino-terminal region of 4.1G. We propose that these dynamic associations provide the structural basis for a regulated molecular adhesive complex that serves to cluster and transport LFA-1 and associated molecules.
Ralston
Kylie J
KJ
Cancer Research Unit, School of Biomedical Sciences, The University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia.
Hird
Samantha L
SL
Zhang
Xinhai
X
Scott
Judith L
JL
Jin
Boquan
B
Thorne
Rick F
RF
Berndt
Michael C
MC
Boyd
Andrew W
AW
Burns
Gordon F
GF
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D001692:Biological Transport; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry / Q000648:ultrastructure; D006224:Cricetinae; D003432:Cross-Linking Reagents; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry*; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000098862:T Lineage-Specific Activation Antigen 1
D048868:Adaptor Proteins, Signal Transducing; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D003432:Cross-Linking Reagents; D003598:Cytoskeletal Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D020033:Protein Isoforms; D011506:Proteins; D011993:Recombinant Fusion Proteins; C028841:erythrocyte membrane band 4.1 protein; D005982:Glutathione Transferase