2003. Role of Rho-family GTPase Cdc42 in polarized expression of lymphocyte appendages

Abstract: Lymphocytes polarize for motility by developing a broad anterior, where lamellipodia arise, and a simple stalk-like posterior appendage, the uropod. Through time-lapse analysis of normal and leukemic human T cells, it was found that this polarized form is maintained by a mechanism that excludes lamellipodia from the uropod. Lamellipo-dia regularly traveled rearward to encroach upon the uropod but disassembled abruptly at the uro-pod border. This exclusion of lamellipodia from the uropod required the Rho-family guanosine triphosphatase Cdc42. Reduction of Cdc42 activ-ity by expression of dominant-negative Cdc42 re-sulted in “two headed ” cells in which lamellipodia persisted at the distal end of the uropod. Random and chemotactic motility were impaired. Increased Cdc42 activity, induced by expression of activated, mutant Cdc42, was accompanied by a general loss of lamellipodia. The results suggest that one role of Cdc42 in lymphocyte motility is to preserve polar-ity by concentrating lamellipodial disassembly sig-nals in the uropod. J. Leukoc. Biol. 73: 830–840