From IFs to wnt signaling via plakoglobin

In 1980 by Kirschner, Gerhart & colleagues re-examined the process by which fertilization induces dorsal-axis in Xenopus. Their studies revealed a sperm-directed microtubule-dependent rotation of the superficial egg cortex with respect to the underlying cytoplasm. This rotation breaks the radial symmetry of the egg.

Mike Danilchick went on to characterize the complex swirls of cytoplasm that result form this rotation.

A second dorsal axis, leading to the formation of a second head, can be induced articifially by a second centrifugation-induced rearrangement.

Around this same time we were studying the function of vimentin, desmin and keratin-type intermediate filaments in Xenopus. We had found that injection of antikeratin antibodies induced a gastrulation defect.

Since keratin filaments are often anchored to desmosomes, we wondered whether the expression of desmosomal components would enhance or suppress the anti-keratin phenotype.

Much to our surprise, we found that the injection of plakoglobin mRNA lead to the induction of a secondary dorsal axis -- similar to the effect of its paralog ß-catenin.

When such embryos were examined by whole-mount immunocytochemistry (or by autoflouorescence when the exogenous polypeptide was tagged with GFP), we found that the polypeptide accumulated at both cell-cell junctions (which was to be expected) and in nuclei (which was not).

A very similar result was reported using ß-catenin RNA by the Gumbiner lab.

These papers provided the first clear evidence that armadillo-like proteins entered the nucleus!

coming eventually : those magical Merriam and Rubenstein years!

Karnovsky, A. & M.W. Klymkowsky. 1995. Anterior axis duplication in Xenopus induced by the over-expression of the cadherin-binding proteins plakoglobin.Proc. Natl. Acad. Sci. USA92: 4522-4526.

Klymkowsky, M.W. & B. Parr. 1995. The body language of cells: the lintimate connection between cell adhesion and behavior. Cell 83:5-8.

Kofron, M., A. Spagnuolo, M.W. Klymkowsky, C. Wylie & J. Heasman. 1997. Catenins have distinct functions in the early Xenopus embryo. Development124: 1553-1560.

Rubenstein, A, J. Merriam, T. & M. W. Klymkowsky. 1997. Localizing the adhesive and signaling functions of plakoglobin. Devel. Genetics 20: 91-102. 

Gelderloos, J.A., L.L. Witcher, P. Cowin & M.W. Klymkowsky. 1997. Plakoglobin: the other ARM of vertebrates, in Cell Adhesion & Intracellular Signaling,  P. Cowin & M.W. Klymkowsky, eds. Landes Bioscience, 13-30.

Klymkowsky, M.W. 1999. Plakophilin, armadillo repeats and nuclear localization. Microscopy Res. & Tech,43:43-54.