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Analysis of institutional authors

Jayo, AsierAuthorMartinez, ConstantinoAuthor

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January 29, 2014
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L718P mutation in the membrane-proximal cytoplasmic tail of beta 3 promotes abnormal alpha IIb beta 3 clustering and lipid microdomain coalescence, and associates with a thrombasthenia-like phenotype

Publicated to:Haematologica. 95 (7): 1158-1166 - 2010-07-01 95(7), DOI: 10.3324/haematol.2009.018572

Authors: Jayo, Asier; Conde, Isabel; Lastres, Pedro; Martinez, Constantino; Rivera, Jose; Vicente, Vicente; Gonzalez-Manchon, Consuelo

Affiliations

Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER - Author
CSIC - Centro de Investigaciones Biologicas (CIB) - Author
Ctr Invest Biol, Dept Cellular & Mol Biol, Madrid 28040, Spain - Author
Univ Murcia, Ctr Hemodonac, Murcia, Spain - Author
Universidad de Murcia - Author
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Abstract

Support for the role of transmembrane and membrane-proximal domains of alpha IIb beta 3 integrin in the maintenance of receptor low affinity comes from mutational studies showing that activating mutations can induce constitutive bi-directional transmembrane signaling.We report the functional characterization of a mutant alpha IIb beta 3 integrin carrying the Leu718Pro mutation in the membrane-proximal region of the beta 3 cytoplasmic domain, identified in heterozygosis in a patient with a severe bleeding phenotype and defective platelet aggregation and adhesion.Transiently transfected cells expressed similar levels of normal and mutant alpha IIb beta 3, but surface expression of mutant alpha v beta 3 was reduced due to its retention in intracellular compartments. Cells stably expressing mutant alpha IIb beta 3 showed constitutive binding to soluble multivalent ligands as well as spontaneous fibrinogen-dependent aggregation, but their response to DTT was markedly reduced. Fibrinogen-adherent cells exhibited a peculiar spreading phenotype with long protrusions. Immunofluorescence analysis revealed the formation of alpha IIb beta 3 clusters underneath the entire cell body and the presence of atypical high-density patches of clustered alpha IIb beta 3 containing encircled areas devoid of integrin that showed decreased affinity for the fluorescent lipid analog DiIC(16) and were disrupted in cholesterol-depleted cells.These findings are consistent with an important role of the membrane-proximal region of beta 3 in modulating alpha IIb beta 3 clustering and lateral redistribution of membrane lipids. Since the beta 3 mutant was associated with a thrombasthenic phenotype in a patient carrying one normal beta 3 allele, these results support a dominant role of clustering in regulating integrin alpha IIb beta 3 functions in vivo.

Keywords

ActivationAdultBloodCell membraneCells, culturedFemaleGrowth-factorHumansIntegrin beta3Membrane lipidsMembrane microdomainsMutation, missenseNecrosis-factor-alphaPhase-separationPlatelet glycoprotein gpiib-iiia complexThrombasthenia

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Haematologica 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, 2010, it was in position 7/66, thus managing to position itself as a Q1 (Primer Cuartil), in the category Hematology.

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: 4.72, 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 Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 32
  • Scopus: 33
  • Europe PMC: 31

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 2025-08-02:

  • 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: 32 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Italy.

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 (JAYO ANDRES, ASIER) .