The CDM protein DOCK2 in lymphocyte migration.
T and B lymphocytes migrate hundreds of micrometers each day to survey the body's lymphoid tissues for antigens. No other mammalian cell type undergoes such extensive and continual movement, raising the question of whether lymphocytes have specializations to support their migratory behavior. This possibility has recently gained support from studies of mice deficient in DOCK2, a member of the Caenorhabditis elegans Ced-5, mammalian DOCK180 and Drosophila melanogaster myoblast city (CDM) family of scaffolding proteins. Migration of lymphocytes, but not other cell types, is severely disrupted in DOCK2-deficient mice. Despite the conserved role of CDM molecules in regulating Rac activation and actin assembly, relatively little is known about how these molecules function. Here, we review the role of DOCK2 in lymphocyte homing to lymphoid tissues and discuss recent findings for other CDM family molecules that provide a basis for understanding how DOCK2 might function in lymphocytes.
Howard Hughes Medical Institute, Dept of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143-0414, USA. kreif@itsa.ucsf.edu
Karin
K
Reif
Jason
J
Cyster
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002465:Cell Movement; D019743:Chemokines, CXC / Q000145:classification / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins / Q000145:classification / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D020830:rac1 GTP-Binding Protein / Q000737:chemistry / Q000502:physiology*
C489642:Bcap31 protein, mouse; D002352:Carrier Proteins; D019743:Chemokines, CXC; C402110:DOCK2 protein, human; C471356:DOCK2 protein, mouse; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D020830:rac1 GTP-Binding Protein