ArticleBlood2008
Genetic perturbation of the putative cytoplasmic membrane-proximal salt bridge aberrantly activates alpha(4) integrins.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation.Nature communications · 2022Article
- Efficient homing of antibody-secreting cells to the bone marrow requires RNA-binding protein ZFP36L1.The Journal of experimental medicine · 2021Article
- Advanced Strategies in Immune Modulation of Cancer Using Lipid-Based Nanoparticles.Frontiers in immunology · 2017Article
- VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.Nature communications · 2016Article
- Action mechanisms of histone deacetylase inhibitors in the treatment of hematological malignancies.Cancer science · 2016Review
- Structural basis of blocking integrin activation and deactivation for anti-inflammation.Journal of biomedical science · 2015Review
- The dual structural roles of the membrane distal region of the α-integrin cytoplasmic tail during integrin inside-out activation.Journal of cell science · 2015Article
- Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool.Nature communications · 2014Article
- Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice.Blood · 2013Article
- Integrin inactivators: balancing cellular functions in vitro and in vivo.Nature reviews. Molecular cell biology · 2013Review
- Tests of integrin transmembrane domain homo-oligomerization during integrin ligand binding and signaling.The Journal of biological chemistry · 2011Article
- Breaching multiple barriers: leukocyte motility through venular walls and the interstitium.Nature reviews. Molecular cell biology · 2010Review
- Essential roles of VLA-4 in the hematopoietic system.International journal of hematology · 2010Review
- The final steps of integrin activation: the end game.Nature reviews. Molecular cell biology · 2010Review
- Kindling the flame of integrin activation and function with kindlins.Current opinion in hematology · 2009Review
- Role of beta7 integrins in intestinal lymphocyte homing and retention.Current molecular medicine · 2009Review
- Integrin function in T-cell homing to lymphoid and nonlymphoid sites: getting there and staying there.Critical reviews in immunology · 2009Review
- Structural basis of transmembrane domain interactions in integrin signaling.Cell adhesion & migrationArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
alpha(4) integrins play a pivotal role in leukocyte migration and tissue-specific homing. The ability of integrins to bind ligand is dynamically regulated by activation-dependent conformational changes triggered in the cytoplasmic domain. An NMR solution structure defined a putative membrane-proximal salt bridge between the alpha(IIb)beta(3) integrin cytoplasmic tails, which restrains integrins in their low-affinity state. However, the physiological importance of this salt bridge in alpha(4) integrin regulation remains to be elucidated. To address this question, we disrupted the salt bridge in murine germ line by mutating the conserved cytoplasmic arginine R(GFFKR) in alpha(4) integrins. In lymphocytes from knock-in mice (alpha(4)-R/A(GFFKR)), alpha(4)beta(1) and alpha(4)beta(7) integrins exhibited constitutively up-regulated ligand binding. However, transmigration of these cells across VCAM-1 and MAdCAM-1 substrates, or across endothelial monolayers, was reduced. Perturbed detachment of the tail appeared to cause the reduced cell migration of alpha(4)-R/A(GFFKR) lymphocytes. In vivo, alpha(4)-R/A(GFFKR) cells exhibited increased firm adhesion to Peyer patch venules but reduced homing to the gut. Our results demonstrate that the membrane-proximal salt bridge plays a critical role in supporting proper alpha(4) integrin adhesive dynamics. Loss of this interaction destabilizes the nonadhesive conformation, and thereby perturbs the properly balanced cycles of adhesion and deadhesion required for efficient cell migration.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.