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Published on: June 22, 2017
Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21
H Kirikoshi1, N Sagara, J Koike
1Genetics Division, National Cancer Center Research Institute, Tsukiji 5-chome, Tokyo, Chuo-ku, 104-0045, Japan.
Abstract:
The WNT receptors, encoded by the Frizzled genes, are implicated in a variety of cellular processes such as cell fate determination, cell polarity control, and malignant transformation. Human Frizzled-4 (FZD4) cDNAs have been cloned and characterized. FZD4 spans a total of 7392 nucleotides and encodes a 537-amino-acid protein with the N-terminal cysteine-rich domain, seven transmembrane domains, and the C-terminal S/T-X-V motif. The FZD4 mRNA of 7.7 kb in size were detected almost ubiquitously in normal human tissues and larger amounts in fetal kidney, adult heart, skeletal muscle, and ovary. Among cancer cell lines, the FZD4 mRNA level was higher in HeLa S3. The FZD4 gene has been mapped to human chromosome 11q14-q21. FZD4 is homologous to FZD9 and FZD10, and overall amino acid identity is as follows: FZD4 vs FZD9, 51.6%; FZD4 vs FZD10, 51.2%; FZD9 vs FZD10, 65.7%. FZD4 consists of two exons, while FZD9 and FZD10 consist of a single exon. FZD4 might belong to rather the independent FZD subfamily than the FZD9-FZD10 subfamily.
Insights
Researchers characterized Human Frizzled-4 (FZD4), a WNT receptor involved in cell processes and cancer. FZD4 mRNA is widely detected in human tissues, with higher levels in certain fetal and adult tissues and in HeLa S3 cancer cells.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- WNT receptors, encoded by Frizzled genes, regulate crucial cellular functions including cell fate, polarity, and transformation.
- Human Frizzled-4 (FZD4) is a WNT receptor family member with known roles in cellular processes.
Purpose of the Study:
- To clone and characterize the human Frizzled-4 (FZD4) cDNA.
- To investigate the expression pattern and chromosomal localization of the FZD4 gene.
- To analyze the evolutionary relationship of FZD4 with other Frizzled family members.
Main Methods:
- cDNA cloning and sequencing
- mRNA expression analysis using Northern blotting
- Gene mapping using chromosomal analysis
- Sequence homology analysis
Main Results:
- Human FZD4 cDNA was cloned, encoding a 537-amino-acid protein with characteristic WNT receptor domains.
- A 7.7 kb FZD4 mRNA was ubiquitously expressed in normal human tissues, with notable abundance in fetal kidney, adult heart, skeletal muscle, and ovary.
- Higher FZD4 mRNA levels were observed in HeLa S3 cancer cells.
- The FZD4 gene was mapped to human chromosome 11q14-q21.
- FZD4 showed significant homology to FZD9 and FZD10, but structural differences (two exons vs. one) suggest it may form an independent subfamily.
Conclusions:
- Human FZD4 is a distinct WNT receptor with a broad tissue distribution and potential involvement in cancer.
- The characterization of FZD4 provides insights into the Frizzled receptor family's structure and evolution.
- FZD4's expression profile suggests roles in both normal development and potentially in malignant transformation.

