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Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells
Natural Killer (NK) cells perform many functions that depend on actin assembly, including adhesion, chemotaxis, lytic synapse assembly and cytolysis. HS1, the hematopoietic homolog of cortactin, binds to Arp2/3 complex and promotes actin assembly by helping to form and stabilize actin filament branc...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344232/ https://www.ncbi.nlm.nih.gov/pubmed/25723543 http://dx.doi.org/10.1371/journal.pone.0118153 |
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author | Mukherjee, Suranjana Kim, Joanna Mooren, Olivia L. Shahan, Stefanie T. Cohan, Megan Cooper, John A. |
author_facet | Mukherjee, Suranjana Kim, Joanna Mooren, Olivia L. Shahan, Stefanie T. Cohan, Megan Cooper, John A. |
author_sort | Mukherjee, Suranjana |
collection | PubMed |
description | Natural Killer (NK) cells perform many functions that depend on actin assembly, including adhesion, chemotaxis, lytic synapse assembly and cytolysis. HS1, the hematopoietic homolog of cortactin, binds to Arp2/3 complex and promotes actin assembly by helping to form and stabilize actin filament branches. We investigated the role of HS1 in transendothelial migration (TEM) by NK cells. Depletion of HS1 led to a decrease in the efficiency of TEM by NK cells, as measured by transwell assays with endothelial cell monolayers on porous filters. Transwell assays involve chemotaxis of NK cells across the filter, so to examine TEM more specifically, we imaged live-cell preparations and antibody-stained fixed preparations, with and without the chemoattractant SDF-1α. We found small to moderate effects of HS1 depletion on TEM, including whether the NK cells migrated via the transcellular or paracellular route. Expression of HS1 mutants indicated that phosphorylation of HS1 tyrosines at positions 222, 378 and 397 was required for rescue in the transwell assay, but HS1 mutations affecting interaction with Arp2/3 complex or SH3-domain ligands had no effect. The GEF Vav1, a ligand of HS1 phosphotyrosine, influenced NK cell transendothelial migration. HS1 and Vav1 also affected the speed of NK cells migrating across the surface of the endothelium. We conclude that HS1 has a role in transendothelial migration of NK cells and that HS1 tyrosine phosphorylation may signal through Vav1. |
format | Online Article Text |
id | pubmed-4344232 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43442322015-03-04 Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells Mukherjee, Suranjana Kim, Joanna Mooren, Olivia L. Shahan, Stefanie T. Cohan, Megan Cooper, John A. PLoS One Research Article Natural Killer (NK) cells perform many functions that depend on actin assembly, including adhesion, chemotaxis, lytic synapse assembly and cytolysis. HS1, the hematopoietic homolog of cortactin, binds to Arp2/3 complex and promotes actin assembly by helping to form and stabilize actin filament branches. We investigated the role of HS1 in transendothelial migration (TEM) by NK cells. Depletion of HS1 led to a decrease in the efficiency of TEM by NK cells, as measured by transwell assays with endothelial cell monolayers on porous filters. Transwell assays involve chemotaxis of NK cells across the filter, so to examine TEM more specifically, we imaged live-cell preparations and antibody-stained fixed preparations, with and without the chemoattractant SDF-1α. We found small to moderate effects of HS1 depletion on TEM, including whether the NK cells migrated via the transcellular or paracellular route. Expression of HS1 mutants indicated that phosphorylation of HS1 tyrosines at positions 222, 378 and 397 was required for rescue in the transwell assay, but HS1 mutations affecting interaction with Arp2/3 complex or SH3-domain ligands had no effect. The GEF Vav1, a ligand of HS1 phosphotyrosine, influenced NK cell transendothelial migration. HS1 and Vav1 also affected the speed of NK cells migrating across the surface of the endothelium. We conclude that HS1 has a role in transendothelial migration of NK cells and that HS1 tyrosine phosphorylation may signal through Vav1. Public Library of Science 2015-02-27 /pmc/articles/PMC4344232/ /pubmed/25723543 http://dx.doi.org/10.1371/journal.pone.0118153 Text en © 2015 Mukherjee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mukherjee, Suranjana Kim, Joanna Mooren, Olivia L. Shahan, Stefanie T. Cohan, Megan Cooper, John A. Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells |
title | Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells |
title_full | Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells |
title_fullStr | Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells |
title_full_unstemmed | Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells |
title_short | Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells |
title_sort | role of cortactin homolog hs1 in transendothelial migration of natural killer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344232/ https://www.ncbi.nlm.nih.gov/pubmed/25723543 http://dx.doi.org/10.1371/journal.pone.0118153 |
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