Unknown

Dataset Information

0

UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion.


ABSTRACT: NK cell's killing is a tightly regulated process under the control of specific cytoskeletal proteins. This includes Wiskott-Aldrich syndrome protein, Wiskott-Aldrich syndrome protein-interacting protein, cofilin, Munc13-4, and nonmuscle myosin IIA (NMIIA). These proteins play a key role in controlling NK-mediated cytotoxicity either via regulating the attachment of lytic granules to the actin-based cytoskeleton or via promoting the cytoskeletal reorganization that is requisite for lytic granule release. UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins that act as chaperones for both conventional and nonconventional myosin. Although we and others have shown that in lower organisms and in mammalian cells NMIIA-associated functions, such as cytokinesis, cell motility, and organelle trafficking, are dependent upon the presence of UNC-45A, its role in NK-mediated functions is largely unknown. In this article, we describe UNC-45A as a key regulator of NK-mediated cell toxicity. Specifically we show that, in human NK cells, UNC-45A localize at the NK cell immunological synapse of activated NK cells and is part of the multiprotein complex formed during NK cell activation. Furthermore, we show that UNC-45A is disposable for NK cell immunological synapse formation and lytic granules reorientation but crucial for lytic granule exocytosis. Lastly, loss of UNC-45A leads to reduced NMIIA binding to actin, suggesting that UNC-45A is a crucial component in regulating human NK cell cytoskeletal dynamics via promoting the formation of actomyosin complexes.

SUBMITTER: Iizuka Y 

PROVIDER: S-EPMC5189640 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion.

Iizuka Yoshie Y   Cichocki Frank F   Sieben Andrew A   Sforza Fabio F   Karim Razaul R   Coughlin Kathleen K   Isaksson Vogel Rachel R   Gavioli Riccardo R   McCullar Valarie V   Lenvik Todd T   Lee Michael M   Miller Jeffrey J   Bazzaro Martina M  

Journal of immunology (Baltimore, Md. : 1950) 20151005 10


NK cell's killing is a tightly regulated process under the control of specific cytoskeletal proteins. This includes Wiskott-Aldrich syndrome protein, Wiskott-Aldrich syndrome protein-interacting protein, cofilin, Munc13-4, and nonmuscle myosin IIA (NMIIA). These proteins play a key role in controlling NK-mediated cytotoxicity either via regulating the attachment of lytic granules to the actin-based cytoskeleton or via promoting the cytoskeletal reorganization that is requisite for lytic granule  ...[more]

Similar Datasets

| S-EPMC3228501 | biostudies-literature
| S-EPMC5716280 | biostudies-literature
| S-EPMC2268177 | biostudies-literature
| S-EPMC2118468 | biostudies-literature
| S-EPMC7803465 | biostudies-literature
| S-EPMC6317751 | biostudies-literature
| S-EPMC3336789 | biostudies-literature
| S-EPMC2823627 | biostudies-literature
| S-EPMC3341559 | biostudies-literature
| S-EPMC4225561 | biostudies-literature