Influence of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 on epithelial differentiation and organization during lung development

Proper development of the respiratory bronchiole and alveolar epithelium proceeds through coordinated cross talk between the interface of epithelium and neighboring mesenchyme. Signals that facilitate and coordinate the cross talk as the bronchial forming canalicular stage transitions to construction of air-exchanging capillary-alveoli niche in the alveolar stage are poorly understood. Expressed within this decisive region, levels of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1) inversely correlate with the maturation of the lung. The present study addresses the role of AIMP1 in lung development through the generation and characterization of Aimp1−/− mutant mice. Mating of Aimp1+/− produced offspring in expected Mendelian ratios throughout embryonic development. However, newborn Aimp1−/− pups exhibited neonatal lethality with mild cyanosis. Imaging both structure and ultrastructure of Aimp1−/− lungs showed disorganized bronchial epithelium, decreased type I but not type II cell differentiation, increased distal vessels, and disruption of E-cadherin deposition in cell-cell junctions. Supporting the in vivo findings of disrupted epithelial cell-cell junctions, in vitro biochemical experiments show that a portion of AIMP1 binds to phosphoinositides, the lipid anchor of proteins that have a fundamental role in both cellular membrane and actin cytoskeleton organization; a dramatic disruption in F-actin cytoskeleton was observed in Aimp1−/− mouse embryonic fibroblasts. Such observed structural defects may lead to disrupted cell-cell boundaries. Together, these results suggest a requirement of AIMP1 in epithelial cell differentiation in proper lung development.

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Contact inhibition of locomotion and mechanical cross-talk between cell–cell and cell–substrate adhesion determine the pattern of junctional tension in epithelial cell aggregates

Molecular Biology of the Cell ◽

10.1091/mbc.e16-04-0226 ◽

2016 ◽

Vol 27 (22) ◽

pp. 3436-3448 ◽

Cited By ~ 17

Author(s):

Luke Coburn ◽

Hender Lopez ◽

Benjamin J. Caldwell ◽

Elliott Moussa ◽

Chloe Yap ◽

...

Keyword(s):

Epithelial Cell ◽

Cross Talk ◽

Contact Inhibition ◽

Cell Junctions ◽

Asymmetric Distribution ◽

Cell Aggregates ◽

Substrate Adhesion ◽

Cell Substrate ◽

Cell Substrate Adhesion ◽

Cell Cell

We used a computational approach to analyze the biomechanics of epithelial cell aggregates—islands, stripes, or entire monolayers—that combines both vertex and contact-inhibition-of-locomotion models to include cell–cell and cell–substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high-order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces, and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell–cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scale up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a three-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical cross-talk, as well as the distribution of principal stress in cells within epithelial cell aggregates. By making experimentally testable predictions, our approach can aid in mechanical analysis of epithelial tissues, especially when local changes in cell–cell and/or cell–substrate adhesion drive collective cell behavior.

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Aminoacyl tRNA synthetase complex interacting multifunctional protein 1 simultaneously binds Glutamyl-Prolyl-tRNA synthetase and scaffold protein aminoacyl tRNA synthetase complex interacting multifunctional protein 3 of the multi-tRNA synthetase complex

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2018.04.015 ◽

2018 ◽

Vol 99 ◽

pp. 197-202 ◽

Cited By ~ 3

Author(s):

Margaret A. Schwarz ◽

Daniel D. Lee ◽

Seamus Bartlett

Keyword(s):

Trna Synthetase ◽

Scaffold Protein ◽

Aminoacyl Trna Synthetase ◽

Multifunctional Protein

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Protein Phosphatase 2A: More Than a Passenger in the Regulation of Epithelial Cell–Cell Junctions

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2019.00030 ◽

2019 ◽

Vol 7 ◽

Cited By ~ 3

Author(s):

Diana Schuhmacher ◽

Jean-Marie Sontag ◽

Estelle Sontag

Keyword(s):

Epithelial Cell ◽

Protein Phosphatase ◽

Protein Phosphatase 2A ◽

Cell Junctions ◽

Phosphatase 2A ◽

Cell Cell

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Serum Aminoacyl-tRNA Synthetase-Interacting Multifunctional Protein-1 Can Predict Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Pilot Monocentric Study

BioMed Research International ◽

10.1155/2019/7508240 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Sung Soo Ahn ◽

Jin-Ock Kim ◽

Taejun Yoon ◽

Jason Jungsik Song ◽

Yong-Beom Park ◽

...

Keyword(s):

Clinical Manifestations ◽

Multivariate Logistic Regression Analysis ◽

Antineutrophil Cytoplasmic Antibody ◽

Population Based ◽

Trna Synthetase ◽

Aminoacyl Trna Synthetase ◽

Serum Samples ◽

Cross Sectional ◽

Multifunctional Protein ◽

Protein Levels

We investigated whether serum aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) could predict severe cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on the Birmingham vasculitis activity score (BVAS). Sixty-one patients with AAV were selected for inclusion from our prospective AAV cohort. AAV-specific indices and clinical manifestations were assessed, and laboratory tests were performed on the day of blood sampling. Patients with severe AAV were defined as those with a BVAS higher than the lower limit of the highest tertile of BVAS (BVAS ≥ 12). We measured serum AIMP1 levels of the stored serum samples. A total of 20 (32.8%) and 41 (67.2%) patients were classified as having severe and nonsevere AAV according to the cut-off of BVAS ≥ 12. Patients with severe AAV showed higher frequencies of general and renal manifestations, along with ANCA positivity, and exhibited a higher mean neutrophil count, erythrocyte sedimentation rate, and C-reactive protein levels, but lower mean haemoglobin and serum albumin levels than those with nonsevere AAV. The mean serum AIMP1 level in patients with severe AAV was significantly higher than that of patients with nonsevere AIMP1 (351.1 vs. 98.4 pg/mL, p = 0.006). Multivariate logistic regression analysis including variables showing significance in univariate analyses revealed that only serum AIMP1 exhibited a significant association with severe AAV (odds ratio 1.004, p = 0.031). When we set the optimal cut-off of serum AIMP1 for severe AAV to 50.28 pg/mL, patients with severe AAV more frequently had AIMP1 levels above the cut-off than those with nonsevere AAV (80.0% vs. 31.7%, relative risk 8.615, p < 0.001). The results from our study suggest that serum AIMP1 can be used to estimate the cross-sectional severe AAV population based on the BVAS.

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Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 suppresses tumor growth in breast cancer-bearing mice by negatively regulating myeloid-derived suppressor cell functions

Cancer Immunology Immunotherapy ◽

10.1007/s00262-015-1777-2 ◽

2015 ◽

Vol 65 (1) ◽

pp. 61-72 ◽

Cited By ~ 11

Author(s):

Hye-Jin Hong ◽

Hui Xuan Lim ◽

Ju Han Song ◽

Arim Lee ◽

Eugene Kim ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Suppressor Cell ◽

Trna Synthetase ◽

Aminoacyl Trna Synthetase ◽

Multifunctional Protein ◽

Cell Functions ◽

Myeloid Derived Suppressor Cell

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Functional Fragments of AIMP1-Derived Peptide (AdP) and Optimized Hydrosol for Their Topical Deposition by Box-Behnken Design

Molecules ◽

10.3390/molecules24101967 ◽

2019 ◽

Vol 24 (10) ◽

pp. 1967 ◽

Cited By ~ 1

Author(s):

Jeong-Jun Lee ◽

Young-Min Han ◽

Tae-Wan Kwon ◽

Dong Hyun Kim ◽

Han Sol Lee ◽

...

Keyword(s):

Near Infrared ◽

Topical Delivery ◽

Trna Synthetase ◽

Functional Domain ◽

Aminoacyl Trna Synthetase ◽

Box Behnken Design ◽

Multifunctional Protein ◽

Domain Mapping ◽

Cosmetic Formulation ◽

Near Infrared Fluorescence Imaging

Aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)-derived peptide (AdP) has been developed as a cosmeceutical ingredient for skin anti-aging given its fibroblast-activating (FA) and melanocyte-inhibiting (MI) functions. However, a suitable strategy for the topical delivery of AdP was required due to its low-permeable properties. In this study, FA and MI domains of AdP (FA-AdP and MI-AdP, respectively) were determined by functional domain mapping, where the activities of several fragments of AdP on fibroblast and melanocyte were tested, and a hydrosol-based topical delivery system for these AdP fragments was prepared. The excipient composition of the hydrosol was optimized to maximize the viscosity and drying rate by using Box-Behnken design. The artificial skin deposition of FA-AdP-loaded hydrosol was evaluated using Keshary-Chien diffusion cells equipped with Strat-M membrane (STM). The quantification of the fluorescent dye-tagged FA-AdP in STM was carried out by near-infrared fluorescence imaging. The optimized hydrosol showed 127-fold higher peptide deposition in STM than free FA-AdP (p < 0.05). This work suggests that FA- and MI-AdP are active-domains for anti-wrinkle and whitening activities, respectively, and the hydrosol could be used as a promising cosmetic formulation for the delivery of AdPs to the skin.

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Chemical suppression of an oncogenic splicing variant of AIMP2 induces tumour regression

Biochemical Journal ◽

10.1042/bj20130550 ◽

2013 ◽

Vol 454 (3) ◽

pp. 411-416 ◽

Cited By ~ 12

Author(s):

Hee Sook Lee ◽

Dae Gyu Kim ◽

Young Sun Oh ◽

Nam Hoon Kwon ◽

Jin Young Lee ◽

...

Keyword(s):

Trna Synthetase ◽

Tumour Regression ◽

Mrna Transcript ◽

Aminoacyl Trna Synthetase ◽

Multifunctional Protein ◽

Splicing Variant ◽

Oncogenic Protein ◽

Small Chemical

A splicing variant of aminoacyl-tRNA synthetase-interacting multifunctional protein 2 (AIMP2-DX2) is a pro-oncogenic protein which is up-regulated in various cancers. We suggest that the small chemical BC-DXI01 can selectively down-regulate the AIMP2-DX2 mRNA transcript and result in tumour regression.

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