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CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion
by
Moiseeva, Elena P.
, Leyland, Mark L.
, Bradding, Peter
in
Adhesion
/ Allergic diseases
/ Allergies
/ Alternative splicing
/ Apoptosis
/ Bcl-x protein
/ Biochemistry
/ Biomedical and Life Sciences
/ Biomedicine
/ Blotting, Western
/ Caspase-3
/ Cell Adhesion
/ Cell adhesion & migration
/ Cell Adhesion Molecule-1
/ Cell adhesion molecules
/ Cell Adhesion Molecules - metabolism
/ Cell Aggregation
/ Cell Biology
/ Cell differentiation
/ Cell Survival
/ Cells, Cultured
/ Down-regulation
/ Exons
/ Humans
/ Immunoglobulins - metabolism
/ Isoforms
/ Leukemia, Mast-Cell - metabolism
/ Leukemia, Mast-Cell - pathology
/ Life Sciences
/ Lung - cytology
/ Lung - metabolism
/ Lungs
/ Mast cells
/ Mast Cells - cytology
/ Mast Cells - metabolism
/ Mast-Cell Sarcoma - metabolism
/ Mast-Cell Sarcoma - pathology
/ Mastocytosis
/ Molecular biology
/ Protein Isoforms
/ Real-Time Polymerase Chain Reaction
/ Research Article
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA, Messenger - genetics
/ Signal transduction
/ Smooth muscle
/ Survival
2012
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CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion
by
Moiseeva, Elena P.
, Leyland, Mark L.
, Bradding, Peter
in
Adhesion
/ Allergic diseases
/ Allergies
/ Alternative splicing
/ Apoptosis
/ Bcl-x protein
/ Biochemistry
/ Biomedical and Life Sciences
/ Biomedicine
/ Blotting, Western
/ Caspase-3
/ Cell Adhesion
/ Cell adhesion & migration
/ Cell Adhesion Molecule-1
/ Cell adhesion molecules
/ Cell Adhesion Molecules - metabolism
/ Cell Aggregation
/ Cell Biology
/ Cell differentiation
/ Cell Survival
/ Cells, Cultured
/ Down-regulation
/ Exons
/ Humans
/ Immunoglobulins - metabolism
/ Isoforms
/ Leukemia, Mast-Cell - metabolism
/ Leukemia, Mast-Cell - pathology
/ Life Sciences
/ Lung - cytology
/ Lung - metabolism
/ Lungs
/ Mast cells
/ Mast Cells - cytology
/ Mast Cells - metabolism
/ Mast-Cell Sarcoma - metabolism
/ Mast-Cell Sarcoma - pathology
/ Mastocytosis
/ Molecular biology
/ Protein Isoforms
/ Real-Time Polymerase Chain Reaction
/ Research Article
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA, Messenger - genetics
/ Signal transduction
/ Smooth muscle
/ Survival
2012
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CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion
by
Moiseeva, Elena P.
, Leyland, Mark L.
, Bradding, Peter
in
Adhesion
/ Allergic diseases
/ Allergies
/ Alternative splicing
/ Apoptosis
/ Bcl-x protein
/ Biochemistry
/ Biomedical and Life Sciences
/ Biomedicine
/ Blotting, Western
/ Caspase-3
/ Cell Adhesion
/ Cell adhesion & migration
/ Cell Adhesion Molecule-1
/ Cell adhesion molecules
/ Cell Adhesion Molecules - metabolism
/ Cell Aggregation
/ Cell Biology
/ Cell differentiation
/ Cell Survival
/ Cells, Cultured
/ Down-regulation
/ Exons
/ Humans
/ Immunoglobulins - metabolism
/ Isoforms
/ Leukemia, Mast-Cell - metabolism
/ Leukemia, Mast-Cell - pathology
/ Life Sciences
/ Lung - cytology
/ Lung - metabolism
/ Lungs
/ Mast cells
/ Mast Cells - cytology
/ Mast Cells - metabolism
/ Mast-Cell Sarcoma - metabolism
/ Mast-Cell Sarcoma - pathology
/ Mastocytosis
/ Molecular biology
/ Protein Isoforms
/ Real-Time Polymerase Chain Reaction
/ Research Article
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA, Messenger - genetics
/ Signal transduction
/ Smooth muscle
/ Survival
2012
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CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion
Journal Article
CADM1 isoforms differentially regulate human mast cell survival and homotypic adhesion
2012
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Overview
Cell adhesion molecule 1 (CADM1), expressed by human lung mast cells (HLMCs), mediates their adhesion to airway smooth muscle (ASM), and contributes to ASM-dependent HLMC proliferation and survival. CADM1 is expressed in alternatively spliced isoforms, but those present in HLMCs and their function are not known. We cloned three functional and one cryptic non-functional isoform with alternative splicing between exons 7/11 and 1/2, respectively, from HLMCs and human MC lines (HMC-1 and LAD2). Differentiated HLMCs and LAD2 cells expressed the functional isoform SP4 containing exons 7/8/11 (~80% of clones), as well as SP1 (exons 7/8/9/11) and a novel SP6 (exons 7/8/9/10/11). In contrast, immature HMC-1 cells expressed only functional SP4. SP4 overexpression in HMC-1 cells and HLMCs augmented homotypic adhesion to a greater extent than SP1 in various conditions. In contrast, CADM1 downregulation abolished homotypic adhesion, indicating that CADM1 is the sole receptor mediating mast cell aggregation. CADM1-mediated adhesion was enhanced by the presence of cell survival factors. SP1 overexpression in HMC-1 cells compromised survival compared to SP4 overexpression or control. CADM1 downregulation resulted in reduced viability and decreased expression of the pro-survival protein Mcl-1
L
, but not Blc-2 or Bcl-X
L
, and increased caspase-3/7 activity in both HMC-1 cells and HLMCs. This coincided with decreased basal Kit levels in HLMCs. In summary, human MCs express multiple CADM1 isoforms which exhibit differential regulation of survival and homotypic adhesion. The most highly expressed SP4 isoform is likely to contribute to MC aggregation and longevity in mastocytosis, and augment the pathophysiology of allergic diseases.
Publisher
SP Birkhäuser Verlag Basel,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Cell Adhesion Molecules - metabolism
/ Exons
/ Humans
/ Immunoglobulins - metabolism
/ Isoforms
/ Leukemia, Mast-Cell - metabolism
/ Leukemia, Mast-Cell - pathology
/ Lungs
/ Mast-Cell Sarcoma - metabolism
/ Mast-Cell Sarcoma - pathology
/ Real-Time Polymerase Chain Reaction
/ Reverse Transcriptase Polymerase Chain Reaction
/ Survival
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