CD29 integrin- and LIMK1/cofilin-mediated actin reorganization regulates the migration of haematopoietic progenitor cells underneath bone marrow stromal cells

Migration and successive homing of haematopoietic stem/progenitor cells (HS/PCs) into haematopoietic microenvironments are critical to their proliferation and differentiation. To investigate molecular mechanisms underlying HS/PC migration, we used a human erythroleukaemia (HEL) cell line which has been characterized as a haematopoietic progenitor cell line and displays high migratory properties underneath the haematopoietic-supportive stromal cell line, HESS-M28. HEL cell migration is mediated by the adhesion of the CD29 integrin on HEL cells to HESS-28 cells which leads to the localization of filamentous actin and formation of cell polarity at membrane protrusions via actin cytoskeleton reorganization. HEL cell migration is inhibited by both dominant negative forms of the Rho-GTPase family members and a cell permeable inhibitor of LIMK1, S3 peptide. Expression of constitutively active- or inactive-forms of cofilin also inhibits HEL cell migration and phosphorylated cofilin is localized to the front protrusions of HEL cells. These results suggest that cytoskeleton reorganization mediated by a Rho-GTPase/LIMK1/cofilin pathway plays a critical role in the migration of HEL cells underneath HESS-M28 cells.