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Dysferlin Is Expressed in Human Placenta But Does Not Associate with Caveolin¹

Departments of Physiology and Cell Biology³ and Obstetrics and Gynecology,⁴ The Ohio State University, Columbus, Ohio 43210 Department of Molecular Anatomy,⁵ Nippon Medical School, Tokyo 113-8602, Japan

ABSTRACT

A proteomics screen of human placental microvillous syncytiotrophoblasts (STBs) revealed the expression of dysferlin (DYSF), a plasma membrane repair protein associated with certain muscular dystrophies. This was unexpected given that previous studies of DYSF have been restricted to skeletal muscle. Within the placenta, DYSF localized to the STB and, with the exception of variable labeling in the fetal placental endothelium, none of the other cell types expressed detectable levels of DYSF. Such restricted expression was recapitulated using primary trophoblast cell cultures, because the syncytia expressed DYSF, but not the prefusion mononuclear cells. The apical plasma membrane of the STB contained 4-fold more DYSF than the basal membrane, suggesting polarized trafficking. Unlike skeletal muscle, DYSF in the STB is localized to the plasma membrane in the absence of caveolin. DYSF expression in the STB was developmentally regulated, because first-trimester placentas expressed 3-fold more DYSF than term placentas. As the current literature indicates that few cell types express DYSF, it is of interest that the two major syncytial structures in the human body, skeletal muscle and the STB, express this protein.

caveolin, dysferlin, placenta, syncytiotrophoblast, trophoblast

¹Supported in part by the National Institutes of Health grants HD38764 (J.M.R) and HD49628 (W.E.A.) and the Ministry of Education, Culture, Sports, and Science grants-in-aid 16390479 and 16659457 (T.T.).

Correspondence: ²John M. Robinson, Department of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210. FAX: 614 292 4888; e-mail: robinson.21{at}osu.edu