The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation
A dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cel...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-05-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2016.1235688 |
| _version_ | 1797684356800577536 |
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| author | Steven G. Thomas Natalie S. Poulter Danai Bem Brenda Finney Laura M. Machesky Stephen P. Watson |
| author_facet | Steven G. Thomas Natalie S. Poulter Danai Bem Brenda Finney Laura M. Machesky Stephen P. Watson |
| author_sort | Steven G. Thomas |
| collection | DOAJ |
| description | A dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cell types. In platelets and megakaryocytes, these proteins have been shown to be important for proper platelet production and function. The cortactin family of proteins (Cttn & HS1) are known to regulate WASp-Arp2/3-mediated actin polymerisation in other cell types and so here we address the role of these proteins in platelets using knockout mouse models. We generated mice lacking Cttn and HS1 in the megakaryocyte/platelet lineage. These mice had normal platelet production, with platelet number, size and surface receptor profile comparable to controls. Platelet function was also unaffected by loss of Cttn/HS1 with no differences observed in a range of platelet function assays including aggregation, secretion, spreading, clot retraction or tyrosine phosphorylation. No effect on tail bleeding time or in thrombosis models was observed. In addition, platelet actin nodules, and megakaryocyte podosomes, actin-based structures known to be dependent on WASp and the Arp2/3 complex, formed normally. We conclude that despite the importance of WASp and the Arp2/3 complex in regulating F-actin dynamics in many cells types, the role of cortactin in their regulation appears to be fulfilled by other proteins in platelets. |
| first_indexed | 2024-03-12T00:28:32Z |
| format | Article |
| id | doaj.art-c01ba86f967c4f1687ca75ef6133c33a |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:28:32Z |
| publishDate | 2017-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-c01ba86f967c4f1687ca75ef6133c33a2023-09-15T10:26:28ZengTaylor & Francis GroupPlatelets0953-71041369-16352017-05-0128437237910.1080/09537104.2016.12356881235688The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formationSteven G. Thomas0Natalie S. Poulter1Danai Bem2Brenda Finney3Laura M. Machesky4Stephen P. Watson5Institute of Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, University of BirminghamInstitute of Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, University of BirminghamInstitute of Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, University of BirminghamInstitute of Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, University of BirminghamUniversity of GlasgowInstitute of Cardiovascular Sciences, Institute for Biomedical Research, The Medical School, University of BirminghamA dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cell types. In platelets and megakaryocytes, these proteins have been shown to be important for proper platelet production and function. The cortactin family of proteins (Cttn & HS1) are known to regulate WASp-Arp2/3-mediated actin polymerisation in other cell types and so here we address the role of these proteins in platelets using knockout mouse models. We generated mice lacking Cttn and HS1 in the megakaryocyte/platelet lineage. These mice had normal platelet production, with platelet number, size and surface receptor profile comparable to controls. Platelet function was also unaffected by loss of Cttn/HS1 with no differences observed in a range of platelet function assays including aggregation, secretion, spreading, clot retraction or tyrosine phosphorylation. No effect on tail bleeding time or in thrombosis models was observed. In addition, platelet actin nodules, and megakaryocyte podosomes, actin-based structures known to be dependent on WASp and the Arp2/3 complex, formed normally. We conclude that despite the importance of WASp and the Arp2/3 complex in regulating F-actin dynamics in many cells types, the role of cortactin in their regulation appears to be fulfilled by other proteins in platelets.http://dx.doi.org/10.1080/09537104.2016.1235688actin nodulescortactinhs1plateletspodosomes |
| spellingShingle | Steven G. Thomas Natalie S. Poulter Danai Bem Brenda Finney Laura M. Machesky Stephen P. Watson The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation Platelets actin nodules cortactin hs1 platelets podosomes |
| title | The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation |
| title_full | The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation |
| title_fullStr | The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation |
| title_full_unstemmed | The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation |
| title_short | The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation |
| title_sort | actin binding proteins cortactin and hs1 are dispensable for platelet actin nodule and megakaryocyte podosome formation |
| topic | actin nodules cortactin hs1 platelets podosomes |
| url | http://dx.doi.org/10.1080/09537104.2016.1235688 |
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