Antibodies differentiate desmosome-form and nucleus-form pinin: evidence that pinin is a moonlighting protein with dual location at the desmosome and within the nucleus.

Pinin is a desmosome-associated protein occurring in epithelia, cardiac muscle, and meninges. This molecule was found to be capable of enhancing cell junction formation and thought to play a key role in reorganization and stabilization of the desmosome-intermediate filament complex in epithelial cells (J. Cell Biol. (1996) 135, 1027-1042). Recently a protein, claimed to be localized exclusively in the nucleus, however, with amino acid sequence identical to pinin, was reported (E. J. Cell Biol. (1998) 75, 295-298). Here I present evidence that pinin exists simultaneously at the desmosome and within the nucleus by generating location-specific monoclonal antibodies. Although the desmosome-form (d-form) and the nucleus-form (n-form) pinin share identical amino acid sequences as demonstrated by cDNA library screening and DNA sequencing, they exhibit remarkably different biochemical properties, reflecting the apparent different multiprotein nature of their differential cellular locations. In addition, the d-form pinin is characterized by a dynamic transport process which involves the gradual diminishing of nuclear materials relative to enhanced anchoring of pinin to the desmosome upon mature cells. Finally I demonstrate that pinin exists in two forms of different gene product: pinin1 and pinin2. These data argue strongly against the statement that pinin is an exclusive nuclear protein and support the notion that pinin is a moonlighting protein with more than one function as a consequence of its dual cellular location.