Neutrophils Lacking Phosphoinositide 3-Kinase γ Show Loss of Directionality during N-formyl-Met-Leu-Phe-Induced Chemotaxis
Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase γ, (PI3K)γ-/-neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kγ-/-neu...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2002-03, Vol.99 (6), p.3603-3608 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3608 |
|---|---|
| container_issue | 6 |
| container_start_page | 3603 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 99 |
| creator | Hannigan, Michael Zhan, Lijun Li, Zhong Ai, Youxi Wu, Dianqing Huang, Chi-Kuang |
| description | Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase γ, (PI3K)γ-/-neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kγ-/-neutrophils failed to translocate up the cheomotactic gradient. A partial reduction in cell motility and abnormal morphologies were also observed. In the wild-type neutrophils, the pleckstrin homology domain-containing protein kinase B (AKT) and F-actin colocalize to the leading edge of polarized neutrophils oriented toward the gradient, which was not observed in PI3Kγ-/-neutrophils. In PI3Kγ-/-neutrophils, AKT staining consistently failed to perfectly overlap with the F-actin. This failure was observed as an F-actin-filled region of 2.3 ± 0.5 µm between AKT and the cell membrane. These data suggest that PI3Kγ regulates neutrophil chemotaxis primarily by controlling the direction of cell migration and the intracellular colocalization of AKT and F-actin to the leading edge. |
| doi_str_mv | 10.1073/pnas.052010699 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pnas_</sourceid><recordid>TN_cdi_pnas_primary_99_6_3603_fulltext</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>3058173</jstor_id><sourcerecordid>3058173</sourcerecordid><originalsourceid>FETCH-LOGICAL-c477t-a369e41f1d2a5f743509cd82f8855ae9c9a42da714fd35311d847c7536fe059b3</originalsourceid><addsrcrecordid>eNqFkctu1DAUhiMEokNhywpQxIKdh-NbHC-6QMOtIpRKwNpyE6fxkMTBdqAjHov34JnwaIahsIDVWfzff25_lt3HsMQg6NNp1GEJnACGQsob2QKDxKhgEm5mCwAiUMkIO8ruhLAGAMlLuJ0dYSyBMUIX2bczM0fvps72Ia90_cmOl_l558LUOTu6YKNtTE7RG5sGmfzH9_x9577mlQshd23-3HpTR-tG3du4yZvZb_1nqHV-2PTorYmoMjM67ww6HZu5Nk2-6szgor6y4W52q9V9MPf29Tj7-PLFh9VrVL17dbp6VqGaCRGRpoU0DLe4IZq3glEOsm5K0pYl59rIWmpGGi0waxvKKcZNyUQtOC1aA1xe0OPsZNd3mi8G09RmjF73avJ20H6jnLbqT2W0nbp0XxQmhAtI_id7v3efZxOiGmyoTd_r0bg5KIHTrILi_4K4JJKCZAl8_Be4drNPTwwqJUlJgSVP0HIH1T5925v2sDEGtQ1fbcNXh_CT4dH1O3_j-7Sv7bc1_pKlVIWiBVDVzn0fzVVM4MN_gUl_sNPXITp_ACjwEgtKfwLJeM2g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201326195</pqid></control><display><type>article</type><title>Neutrophils Lacking Phosphoinositide 3-Kinase γ Show Loss of Directionality during N-formyl-Met-Leu-Phe-Induced Chemotaxis</title><source>MEDLINE</source><source>Jstor Complete Legacy</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Hannigan, Michael ; Zhan, Lijun ; Li, Zhong ; Ai, Youxi ; Wu, Dianqing ; Huang, Chi-Kuang</creator><creatorcontrib>Hannigan, Michael ; Zhan, Lijun ; Li, Zhong ; Ai, Youxi ; Wu, Dianqing ; Huang, Chi-Kuang</creatorcontrib><description>Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase γ, (PI3K)γ-/-neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kγ-/-neutrophils failed to translocate up the cheomotactic gradient. A partial reduction in cell motility and abnormal morphologies were also observed. In the wild-type neutrophils, the pleckstrin homology domain-containing protein kinase B (AKT) and F-actin colocalize to the leading edge of polarized neutrophils oriented toward the gradient, which was not observed in PI3Kγ-/-neutrophils. In PI3Kγ-/-neutrophils, AKT staining consistently failed to perfectly overlap with the F-actin. This failure was observed as an F-actin-filled region of 2.3 ± 0.5 µm between AKT and the cell membrane. These data suggest that PI3Kγ regulates neutrophil chemotaxis primarily by controlling the direction of cell migration and the intracellular colocalization of AKT and F-actin to the leading edge.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.052010699</identifier><identifier>PMID: 11904423</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Actins ; Actins - metabolism ; Akt protein ; Animals ; Biological Sciences ; Cell membranes ; Cell motility ; Cellular biology ; Centroids ; Chemotaxis ; Chemotaxis, Leukocyte - drug effects ; Class Ib Phosphatidylinositol 3-Kinase ; Cytoskeleton - drug effects ; Cytoskeleton - metabolism ; F-actin ; Gene Deletion ; Histograms ; Imaging ; Isoenzymes - deficiency ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Lipids ; Mice ; Microscopy, Video ; N-Formylmethionine Leucyl-Phenylalanine - pharmacology ; Neutrophils ; Neutrophils - cytology ; Neutrophils - drug effects ; Neutrophils - enzymology ; Phosphatidylinositol 3-Kinases - deficiency ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphatidylinositols ; Polymerization ; Protein-Serine-Threonine Kinases ; Proteins ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-akt ; Scientific imaging</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2002-03, Vol.99 (6), p.3603-3608</ispartof><rights>Copyright 1993-2002 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Mar 19, 2002</rights><rights>Copyright © 2002, The National Academy of Sciences 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-a369e41f1d2a5f743509cd82f8855ae9c9a42da714fd35311d847c7536fe059b3</citedby><cites>FETCH-LOGICAL-c477t-a369e41f1d2a5f743509cd82f8855ae9c9a42da714fd35311d847c7536fe059b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/99/6.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3058173$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3058173$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11904423$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hannigan, Michael</creatorcontrib><creatorcontrib>Zhan, Lijun</creatorcontrib><creatorcontrib>Li, Zhong</creatorcontrib><creatorcontrib>Ai, Youxi</creatorcontrib><creatorcontrib>Wu, Dianqing</creatorcontrib><creatorcontrib>Huang, Chi-Kuang</creatorcontrib><title>Neutrophils Lacking Phosphoinositide 3-Kinase γ Show Loss of Directionality during N-formyl-Met-Leu-Phe-Induced Chemotaxis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase γ, (PI3K)γ-/-neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kγ-/-neutrophils failed to translocate up the cheomotactic gradient. A partial reduction in cell motility and abnormal morphologies were also observed. In the wild-type neutrophils, the pleckstrin homology domain-containing protein kinase B (AKT) and F-actin colocalize to the leading edge of polarized neutrophils oriented toward the gradient, which was not observed in PI3Kγ-/-neutrophils. In PI3Kγ-/-neutrophils, AKT staining consistently failed to perfectly overlap with the F-actin. This failure was observed as an F-actin-filled region of 2.3 ± 0.5 µm between AKT and the cell membrane. These data suggest that PI3Kγ regulates neutrophil chemotaxis primarily by controlling the direction of cell migration and the intracellular colocalization of AKT and F-actin to the leading edge.</description><subject>Actins</subject><subject>Actins - metabolism</subject><subject>Akt protein</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cell membranes</subject><subject>Cell motility</subject><subject>Cellular biology</subject><subject>Centroids</subject><subject>Chemotaxis</subject><subject>Chemotaxis, Leukocyte - drug effects</subject><subject>Class Ib Phosphatidylinositol 3-Kinase</subject><subject>Cytoskeleton - drug effects</subject><subject>Cytoskeleton - metabolism</subject><subject>F-actin</subject><subject>Gene Deletion</subject><subject>Histograms</subject><subject>Imaging</subject><subject>Isoenzymes - deficiency</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Lipids</subject><subject>Mice</subject><subject>Microscopy, Video</subject><subject>N-Formylmethionine Leucyl-Phenylalanine - pharmacology</subject><subject>Neutrophils</subject><subject>Neutrophils - cytology</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - enzymology</subject><subject>Phosphatidylinositol 3-Kinases - deficiency</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphatidylinositols</subject><subject>Polymerization</subject><subject>Protein-Serine-Threonine Kinases</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-akt</subject><subject>Scientific imaging</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhiMEokNhywpQxIKdh-NbHC-6QMOtIpRKwNpyE6fxkMTBdqAjHov34JnwaIahsIDVWfzff25_lt3HsMQg6NNp1GEJnACGQsob2QKDxKhgEm5mCwAiUMkIO8ruhLAGAMlLuJ0dYSyBMUIX2bczM0fvps72Ia90_cmOl_l558LUOTu6YKNtTE7RG5sGmfzH9_x9577mlQshd23-3HpTR-tG3du4yZvZb_1nqHV-2PTorYmoMjM67ww6HZu5Nk2-6szgor6y4W52q9V9MPf29Tj7-PLFh9VrVL17dbp6VqGaCRGRpoU0DLe4IZq3glEOsm5K0pYl59rIWmpGGi0waxvKKcZNyUQtOC1aA1xe0OPsZNd3mi8G09RmjF73avJ20H6jnLbqT2W0nbp0XxQmhAtI_id7v3efZxOiGmyoTd_r0bg5KIHTrILi_4K4JJKCZAl8_Be4drNPTwwqJUlJgSVP0HIH1T5925v2sDEGtQ1fbcNXh_CT4dH1O3_j-7Sv7bc1_pKlVIWiBVDVzn0fzVVM4MN_gUl_sNPXITp_ACjwEgtKfwLJeM2g</recordid><startdate>20020319</startdate><enddate>20020319</enddate><creator>Hannigan, Michael</creator><creator>Zhan, Lijun</creator><creator>Li, Zhong</creator><creator>Ai, Youxi</creator><creator>Wu, Dianqing</creator><creator>Huang, Chi-Kuang</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><general>The National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20020319</creationdate><title>Neutrophils Lacking Phosphoinositide 3-Kinase γ Show Loss of Directionality during N-formyl-Met-Leu-Phe-Induced Chemotaxis</title><author>Hannigan, Michael ; Zhan, Lijun ; Li, Zhong ; Ai, Youxi ; Wu, Dianqing ; Huang, Chi-Kuang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-a369e41f1d2a5f743509cd82f8855ae9c9a42da714fd35311d847c7536fe059b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Actins</topic><topic>Actins - metabolism</topic><topic>Akt protein</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>Cell membranes</topic><topic>Cell motility</topic><topic>Cellular biology</topic><topic>Centroids</topic><topic>Chemotaxis</topic><topic>Chemotaxis, Leukocyte - drug effects</topic><topic>Class Ib Phosphatidylinositol 3-Kinase</topic><topic>Cytoskeleton - drug effects</topic><topic>Cytoskeleton - metabolism</topic><topic>F-actin</topic><topic>Gene Deletion</topic><topic>Histograms</topic><topic>Imaging</topic><topic>Isoenzymes - deficiency</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Lipids</topic><topic>Mice</topic><topic>Microscopy, Video</topic><topic>N-Formylmethionine Leucyl-Phenylalanine - pharmacology</topic><topic>Neutrophils</topic><topic>Neutrophils - cytology</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - enzymology</topic><topic>Phosphatidylinositol 3-Kinases - deficiency</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphatidylinositols</topic><topic>Polymerization</topic><topic>Protein-Serine-Threonine Kinases</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-akt</topic><topic>Scientific imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hannigan, Michael</creatorcontrib><creatorcontrib>Zhan, Lijun</creatorcontrib><creatorcontrib>Li, Zhong</creatorcontrib><creatorcontrib>Ai, Youxi</creatorcontrib><creatorcontrib>Wu, Dianqing</creatorcontrib><creatorcontrib>Huang, Chi-Kuang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hannigan, Michael</au><au>Zhan, Lijun</au><au>Li, Zhong</au><au>Ai, Youxi</au><au>Wu, Dianqing</au><au>Huang, Chi-Kuang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neutrophils Lacking Phosphoinositide 3-Kinase γ Show Loss of Directionality during N-formyl-Met-Leu-Phe-Induced Chemotaxis</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2002-03-19</date><risdate>2002</risdate><volume>99</volume><issue>6</issue><spage>3603</spage><epage>3608</epage><pages>3603-3608</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase γ, (PI3K)γ-/-neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kγ-/-neutrophils failed to translocate up the cheomotactic gradient. A partial reduction in cell motility and abnormal morphologies were also observed. In the wild-type neutrophils, the pleckstrin homology domain-containing protein kinase B (AKT) and F-actin colocalize to the leading edge of polarized neutrophils oriented toward the gradient, which was not observed in PI3Kγ-/-neutrophils. In PI3Kγ-/-neutrophils, AKT staining consistently failed to perfectly overlap with the F-actin. This failure was observed as an F-actin-filled region of 2.3 ± 0.5 µm between AKT and the cell membrane. These data suggest that PI3Kγ regulates neutrophil chemotaxis primarily by controlling the direction of cell migration and the intracellular colocalization of AKT and F-actin to the leading edge.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>11904423</pmid><doi>10.1073/pnas.052010699</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2002-03, Vol.99 (6), p.3603-3608 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pnas_primary_99_6_3603_fulltext |
| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Actins Actins - metabolism Akt protein Animals Biological Sciences Cell membranes Cell motility Cellular biology Centroids Chemotaxis Chemotaxis, Leukocyte - drug effects Class Ib Phosphatidylinositol 3-Kinase Cytoskeleton - drug effects Cytoskeleton - metabolism F-actin Gene Deletion Histograms Imaging Isoenzymes - deficiency Isoenzymes - genetics Isoenzymes - metabolism Lipids Mice Microscopy, Video N-Formylmethionine Leucyl-Phenylalanine - pharmacology Neutrophils Neutrophils - cytology Neutrophils - drug effects Neutrophils - enzymology Phosphatidylinositol 3-Kinases - deficiency Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Phosphatidylinositols Polymerization Protein-Serine-Threonine Kinases Proteins Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-akt Scientific imaging |
| title | Neutrophils Lacking Phosphoinositide 3-Kinase γ Show Loss of Directionality during N-formyl-Met-Leu-Phe-Induced Chemotaxis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T14%3A12%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pnas_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neutrophils%20Lacking%20Phosphoinositide%203-Kinase%20%CE%B3%20Show%20Loss%20of%20Directionality%20during%20N-formyl-Met-Leu-Phe-Induced%20Chemotaxis&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Hannigan,%20Michael&rft.date=2002-03-19&rft.volume=99&rft.issue=6&rft.spage=3603&rft.epage=3608&rft.pages=3603-3608&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.052010699&rft_dat=%3Cjstor_pnas_%3E3058173%3C/jstor_pnas_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201326195&rft_id=info:pmid/11904423&rft_jstor_id=3058173&rfr_iscdi=true |