TJ Proteins That Make Round Trips to the Nucleus

Abstract

The tight junction (TJ) located at the lirnit between the apical and basolateral plasma rnernbranes, is a multiprotein cornplex integrated by both integral and corticai proteins. Through TJ epithelial cells establish a link with their neighbors that seals the paracellular pathway. Lately sorne TJ proteins like the MAGUK ZO-1 and 20-2, MAGI lc, as well as the unrelated proteins synplekin and ubinuclein, have been found to concentrate at the nucleus. In this chapter we describe such proteins and how their arrival to the nucleus is connected to the degree of cell-ceil contact. We analyze the signals present in theseTJ proteins that rnay be responsible for their rnovernent frorn the mernbrane to the nucleus and vice-versa. We then detail, the interaction of these ~roteins to nuclear rnolecules involved in eene " transcription, chrornatin rernodeling, RNA processing and polyadenylation. In recent times, el1 biologists have begun to recognize the dual location of certain proteins within the same cells. Such proteins appear to work as general constituents of two distant and different structures: they work as subrnernbranous cornponents of intercellular junctions and are also located in karyoplasrns, Cajal bodies, or spliceosornes even in cells devoid of cell-cell junctions. Such proteins have recently been referred as NACos, for proteins that can localize to the nudeus and adhesion cornplexes.' This chapter will deal with TJ proteins that shuttle between the plasma rnernbrane and the nudeus. In al1 the cases so far studied, the subcellular distribution of theTJ NACO proteins is sensitive to the degree of cell-cell contact. Thus in epithelia cultured in a sparse condition, TJ NACos concentrate at the nucleus, whereas in a confluent state, they accurnulate at the TJ and only a negligible proportion is rnaintained at the nucleus. Such behavior suggests that these proteins that rnediate intercellular adhesion, also transrnit inforrnation to the cell interior about the environrnent, such as the la& of neighboring cells. This inforrnation is crucial for deter- rnining epithelial behavior, especially for keeping the balance between proliferation and differ- entiation.