A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts.
Recognition of antigen by T cells requires the formation of a specialized junction between the T cell and the antigen-presenting cell. This junction is generated by the recruitment and the exclusion of specific proteins from the contact area. The mechanisms that regulate these events are unknown. Here we demonstrate that ligand engagement of the adhesion molecule, CD2, initiates a process of protein segregation, CD2 clustering, and cytoskeletal polarization. Although protein segregation was not dependent on the cytoplasmic domain of CD2, CD2 clustering and cytoskeletal polarization required an interaction of the CD2 cytoplasmic domain with a novel SH3-containing protein. This novel protein, called CD2AP, is likely to facilitate receptor patterning in the contact area by linking specific adhesion receptors to the cytoskeleton.
Dustin
M L
ML
Department of Pathology and Center for Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
Olszowy
M W
MW
Holdorf
A D
AD
Li
J
J
Bromley
S
S
Desai
N
N
Widder
P
P
Rosenberger
F
F
van der Merwe
P A
PA
Allen
P M
PM
Shaw
A S
AS
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D018801:CD2 Antigens / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D003593:Cytoplasm / Q000737:chemistry; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D011940:Receptor Aggregation; D011956:Receptors, Cell Surface / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D018909:src Homology Domains / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D018801:CD2 Antigens; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D008024:Ligands; D011506:Proteins; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear