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2017 ; 28
(4
): 372-379
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The actin binding proteins cortactin and HS1 are dispensable for platelet actin
nodule and megakaryocyte podosome formation
#MMPMID27778524
Thomas SG
; Poulter NS
; Bem D
; Finney B
; Machesky LM
; Watson SP
Platelets
2017[Jun]; 28
(4
): 372-379
PMID27778524
show ga
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.