Distinct roles for the actin nucleators Arp2/3 and hDia1 during NK-mediated cytotoxicity.
BACKGROUND
Several actin nucleators, including Arp2/3 and various formins, control numerous cytoskeletal-based functions in vivo.


RESULTS
We investigated the relative roles of these nucleators. As a model system, we used natural killer (NK) lymphocytes, which display a wide range of cytoskeletal-based functions that culminate in the lysis of target cells. NK cells lacking either Arp2/3 or the formin hDia1 were ineffective in target cell lysis, but for distinct reasons. Loss of Arp2/3 function led to defects in cell adhesion and actin assembly at the junction with the target cell (the lytic synapse). In contrast, loss of hDia1 did not disrupt actin assembly at the lytic synapse. Instead, loss of hDia1 led to perturbations in the microtubule cytoskeleton, including the targeting of microtubules to the lytic synapse.


CONCLUSIONS
These studies reveal novel distinctions and relationships among the functions of Arp2/3, formins, and microtubules in cells. Notably, a formin mediates the capture of microtubules at the cell periphery.
Butler
Boyd
B
Department of Cell Biology and Physiology, Washington University in St. Louis, MO 63110, USA. boyd.butler@wustl.edu
Cooper
John A
JA
D051376:Actin-Related Protein 2-3 Complex / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D000080865:Formins; D006801:Humans; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D015398:Signal Transduction
D051376:Actin-Related Protein 2-3 Complex; D048868:Adaptor Proteins, Signal Transducing; C108962:DIAPH1 protein, human; D005353:Fibronectins; D000080865:Formins; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1