A leucine zipper in the N terminus confers membrane association to SLP-65.
Membrane recruitment of adaptor proteins is crucial for coupling antigen receptors to downstream signaling events. Despite the essential function of the B cell adaptor SLP-65, the mechanism of its recruitment to the plasma membrane is not yet understood. Here we show that a highly conserved leucine zipper in the SLP-65 N terminus is responsible for membrane association. Alterations in the N terminus abolished SLP-65 membrane localization and activity, both of which were restored by replacement of the N terminus with a myristoylation signal. The N terminus is an autonomous domain that confers specific localization and function when transferred to green fluorescent protein or the adaptor protein SLP-76. Our data elucidate the mechanism of SLP-65 membrane recruitment and suggest that leucine zipper motifs are essential interaction domains of signaling proteins.
Köhler
Fabian
F
Institute for Biology III, Albert-Ludwigs University of Freiburg and Max-Planck-Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
Storch
Bettina
B
Kulathu
Yogesh
Y
Herzog
Sebastian
S
Kuppig
Stephan
S
Reth
Michael
M
Jumaa
Hassan
H
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D016350:Leucine Zippers; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019814:Myristic Acid / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; C092947:SLP-76 signal Transducing adaptor proteins; D019814:Myristic Acid