The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation

Thomas, S. G., Poulter, N. S., Bem, D., Finney, B., Machesky, L. M. and Watson, S. P. (2017) The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation. Platelets, 28(4), pp. 372-379. (doi: 10.1080/09537104.2016.1235688) (PMID:27778524) (PMCID:PMC5274539)

Abstract

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.

• Item Type: Articles
• Additional Information: The authors thank the British Heart Foundation for funding (NH/11/6/29061) andthe Biomedical Services Unit (BMSU) at the University of Birminghamfor support with mouse colonies. SPW is a BHF Chair (CH/03/003).LMM is funded by CRUK Core grant A15673.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Machesky, Professor Laura
• Authors: Thomas, S. G., Poulter, N. S., Bem, D., Finney, B., Machesky, L. M., and Watson, S. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Platelets
• Publisher: Taylor & Francis
• ISSN: 0953-7104
• ISSN (Online): 1369-1635
• Published Online: 25 October 2016
• Copyright Holders: Copyright © 2016 Stephen G. Thomas, Natalie S. Poulter, Danai Bem, Brenda Finney, Laura M. Machesky, and Stephen P. Watson
• First Published: First published in Platelets 28(4): 372-379
• Publisher Policy: Reproduced under a Creative Commons License