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Analysis of institutional authors

Hurtado BAuthorSanz-Castillo BAuthorSánchez-Martínez RAuthorGarcia De Frutos PAuthor
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Article

Thrombocytopenia-associated mutations in Ser/Thr kinase MASTL deregulate actin cytoskeletal dynamics in platelets

Publicated to:Journal Of Clinical Investigation. 128 (12): 5351-5367 - 2018-12-03 128(12), DOI: 10.1172/jci121876

Authors: Hurtado, Begona; Trakala, Marianna; Ximenez-Embun, Pilar; El Bakkali, Aicha; Partida, David; Sanz-Castillo, Belen; Alvarez-Fernandez, Monica; Maroto, Maria; Sanchez-Martinez, Ruth; Martinez, Lola; Munoz, Javier; Garcia de Frutos, Pablo; Malumbres, Marcos

Affiliations

CNIO, Cytometry Unit, Madrid, Spain      Spanish National Cancer Research Centre - Author
CNIO, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain.      Spanish National Cancer Research Centre - Author
CNIO, Prote Unit, Madrid, Spain      Spanish National Cancer Research Centre - Author
Inst Investt Biomed August Pi & Sunyer IIBB CSIC, Dept Cell Death & Proliferat, Inst Invest Biomed Barcelona, CSIC, Barcelona, Spain      Consejo Superior de Investigaciones Cientificas (CSIC)    University of Barcelona    CSIC - Instituto de Investigaciones Biomedicas de Barcelona (IIBB)       - Author
ProteoRed Inst Salud Carlos III ISCIII, Madrid, Spain - Author
Spanish Natl Canc Res Ctr CNIO, Canc Grp, Madrid, Spain      Spanish National Cancer Research Centre - Author
Spanish Natl Canc Res Ctr CNIO, Cell Div, Madrid, Spain      Spanish National Cancer Research Centre - Author
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Abstract

MASTL, a Ser/Thr kinase that inhibits PP2A-B55 complexes during mitosis, is mutated in autosomal dominant thrombocytopenia. However, the connections between the cell-cycle machinery and this human disease remain unexplored. We report here that, whereas Mastl ablation in megakaryocytes prevented proper maturation of these cells, mice carrying the thrombocytopenia-associated mutation developed thrombocytopenia as a consequence of aberrant activation and survival of platelets. Activation of mutant platelets was characterized by hyperstabilized pseudopods mimicking the effect of PP2A inhibition and actin polymerization defects. These aberrations were accompanied by abnormal hyperphosphorylation of multiple components of the actin cytoskeleton and were rescued both in vitro and in vivo by inhibiting upstream kinases such as PKA, PKC, or AMPK. These data reveal an unexpected role of Mastl in actin cytoskeletal dynamics in postmitotic cells and suggest that the thrombocytopenia-associated mutation in MASTL is a pathogenic dominant mutation that mimics decreased PP2A activity resulting in altered phosphorylation of cytoskeletal regulatory pathways.

Keywords
Actin cytoskeletonAmino acid substitutionAnimalsBlood plateletsCell biologyCell cycleChromosome breakageChromosome disordersGreatwall protein, mouseHematologyMiceMice, transgenicMicrotubule-associated proteinsMutation, missensePhosphoprotein phosphatasesPhosphorylationProtein serine-threonine kinasesSignal transductionThrombocytopeniaThrombosis

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Clinical Investigation due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2018, it was in position 3/136, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, Research & Experimental. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.71, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-14, the following number of citations:

  • WoS: 19
  • Scopus: 22
  • Europe PMC: 14
  • OpenCitations: 22
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-14:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 31.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 31 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 56.4.
  • The number of mentions on the social network X (formerly Twitter): 12 (Altmetric).
Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Hurtado Villarejo, Begona) .