1992 Fiscal Year Final Research Report Summary
Analysis for the Expressional Change of Caldesmon Isoforms during Phenotyptic Modulation of Smooth Muscle Cells
| Project/Area Number |
03454151
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
SOBUE Kenji Osaka University Medical School, Department of Neurochemistry and Neuropharmacology, Professor, 医学部, 教授 (20112047)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Ken'ichiro Osaka University Medical School, Department of Neurochemistry and Neuropharmacol, 医学部, 助手 (90238105)
TANAKA Junya Osaka University Medical School, Department of Neuropharmacology, Assistant Prof, 医学部, 助手 (70217040)
INUI Makoto Osaka University Medical School, Department of Neurochemistry and Neuropharmacol, 医学部, 助手 (70223237)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Caldesmon / Actin / Calumodulin / Tropomyosin / Smooth muscle / Phenotyptic modulation / Chromosome / Alternative splicing |
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| Research Abstract |
The high Mr caldesmon (h-CaD) is predominantly expressed in smooth muscles, whereas the low Mr caldesmon (l-CaD) is widely distributed in nonmuscle tissues and cells. Their expressional changes are closely correlated with the phenotypic modulation of smooth muscle cells. During a search for the isoform diversity of human CaDs, novel l-CaD cDNAs were cloned from HeLa S3 cell; HeLa l-CaD I is composed of 558 amino acids, whereas 26 amino acids (residues 202-227 for HeLa l-CaD I) are deleted in HeLal-CaD II. The short NH_2-terminal sequence of HeLa l-CaDs is different from that of fibroblast (WI-38) l-CaD II and human aorta h- CaD. We have also analysed the CaD isoforms expressed in human culture cells by RT-PCR. As these results, human l-CaDs are divided into two groups (Hela-and WI-38-types) by its short NH_2-terminal sequences and they are also subdivided to type I with a 26 amino acid insertion and type II without it. To reveal the molecular events of the expressional regulation of the CaD isoforms, the genomic construction of human CaD was determined. The human CaD gene is at least composed of 14 exons, and is mapped to a single locus, 7q33-q34. The 26 amino acid insertion is encoded in exon 4, and is specifically spliced in the mRNAs for both h-CaD and l-CaD Is. Exon 3 is the unique exon which encodes the central repeating domain specific to h-CaD (residues 208-436) together with the common domain in all CaDs(residues 73-207 for h-CaD or WI-38 l-CaDs, and 68-201 for HeLa l-CaDs). The expressional regulation of h-or l-CaD is thought to depend on selection of the two 5'-splice sites within exon 3.Thus, the change in expression between l-and h-CaDs might be caused by this splicing pathway.
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