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J. Cell Biol.,
Volume 140, Number 4, February 23, 1998 767-777
Receptors: Homodimers Form in the ER
and Persist at the Plasma Membrane
§

* Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Abstract. Transforming growth factor
The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142; § Department of Medicine, Brigham and
Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and
Department of Biology, Massachusetts
Institute of Technology, Cambridge, Massachusetts 02139
(TGF-
) signaling involves interactions of at least two different receptors, types I (T
RI) and II (T
RII), which form
ligand-mediated heteromeric complexes. Although we
have shown in the past that T
RII in the absence of
ligand is a homodimer on the cell surface, T
RI has not
been similarly investigated, and the site of complex formation is not known for either receptor. Several studies
have indicated that homomeric interactions are involved in TGF-
signaling and regulation, emphasizing
the importance of a detailed understanding of the homooligomerization of T
RI or T
RII. Here we have
combined complementary approaches to study these
homomeric interactions in both naturally expressing
cell lines and cells cotransfected with various combinations of epitope-tagged type I or type II receptors. We
used sedimentation velocity of metabolically labeled receptors on sucrose gradients to show that both T
RI
and T
RII form homodimer-sized complexes in the
endoplasmic reticulum, and we used coimmunoprecipitation studies to demonstrate the existence of type I homooligomers. Using a technique based on antibody-mediated immunofluorescence copatching of receptors
carrying different epitope tags, we have demonstrated
ligand-independent homodimers of T
RI on the surface of live cells. Soluble forms of both receptors are secreted as monomers, indicating that the ectodomains
are not sufficient to mediate homodimerization, although TGF-
1 is able to promote dimerization of the
type II receptor ectodomain. These findings may have
important implications for the regulation of TGF-
signaling.
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