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Two alternatively spliced mouse urokinase receptor mRNAs with different histological localization in the
P Kristensen1, J Eriksen, F Blasi
1Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Abstract:
Two mouse urokinase-type plasminogen activator receptor (muPAR) cDNAs were isolated: muPAR1 is homologous to the human urokinase-type plasminogen activator receptor while muPAR2 codes for a 199 residue protein sharing the first 133 residues with muPAR1. Mouse genomic DNA sequencing indicates that the two different mRNAs arise by alternative splicing. In situ hybridization showed differential expression of the two mRNAs in mouse gastric mucosa. muPAR1 mRNA is located in luminal epithelial cells situated close to urokinase-type plasminogen activator-producing connective tissue cells of the lamina propria, pointing to plasmin generation controlled by the cooperation of different cells that may play a role in the release of gastric epithelial cells. muPAR2 mRNA is expressed in the basal epithelial cells, and the deduced protein sequence includes the receptor ligand binding domain, but omits the region involved in glycolipid-mediated membrane anchoring, suggesting that muPAR2 may code for a secreted uPA binding protein.
Insights
Researchers discovered two mouse urokinase-type plasminogen activator receptor (muPAR) variants, muPAR1 and muPAR2, arising from alternative splicing. Differential expression in gastric mucosa suggests distinct roles in cell signaling and potential plasmin generation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The urokinase-type plasminogen activator receptor (uPAR) plays a role in cell signaling and extracellular matrix remodeling.
- Understanding uPAR function in different tissues is crucial for deciphering its physiological and pathological roles.
- Alternative splicing is a common mechanism for generating protein diversity from a single gene.
Purpose of the Study:
- To identify and characterize mouse urokinase-type plasminogen activator receptor (muPAR) cDNAs.
- To investigate the expression patterns of different muPAR variants in mouse gastric mucosa.
- To elucidate the potential functional implications of distinct muPAR isoforms.
Main Methods:
- Isolation and sequencing of mouse urokinase-type plasminogen activator receptor (muPAR) cDNAs.
- Analysis of mouse genomic DNA to determine the origin of different muPAR mRNAs.
- In situ hybridization to localize muPAR mRNA expression in mouse gastric tissue.
Main Results:
- Two distinct muPAR cDNAs, muPAR1 and muPAR2, were identified.
- Genomic analysis revealed that muPAR1 and muPAR2 result from alternative splicing of the same gene.
- Differential expression of muPAR1 and muPAR2 mRNAs was observed in the mouse gastric mucosa, with muPAR1 in luminal epithelial cells and muPAR2 in basal epithelial cells.
Conclusions:
- Alternative splicing generates at least two distinct muPAR variants in mice.
- The differential expression of muPAR1 and muPAR2 in gastric mucosa suggests specialized functions.
- muPAR1's localization points to a role in cell cooperation for plasmin generation, while muPAR2 may function as a secreted uPA binding protein.