Regulation of leukocyte motility by ELMO family proteins
Time-lapse imaging of CD4+ T cells from wild-type (WT, CFSE) and Elmo1-/- (KO, TAMRA) crawling on a glass dish coated with ICAM-1 and CCL21.
Mammalian ELMO proteins (ELMO1-3, Engulfment and Cell Motility) are a family of evolutionarily conserved cytoplasmic adaptor proteins that bind to Dock proteins to promote the activation of the small GTPase Rac â€“ a critical regulator of actin polymerization, cell shape and motility. Using Elmo1-deficient mice we have recently discovered a critical and non-redundant role for Elmo1 in regulating chemotaxis of naÃ¯ve T cells to CCR7 and CXCR4 ligands.
The overall goal of this project is to understand how Elmo1 functions to promote T cell migration and what role Elmo1 plays in T cell trafficking during adaptive immune responses. We have several active areas of investigation related to Elmo1 function: 1) determine how Elmo1 functions within T cells to integrate extracellular cues to affect cytoskeletal changes and cell migration, 2) assess the unique and overlapping functions of the three mammalian ELMO family members in lymphocytes, 3) determine the role of Elmo1 in controlling T cell migration into tissues during an immune response. These studies are aimed at developing new approaches to target the Elmo-Dock-Rac module to control T cell trafficking in diseased tissues.
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