AF6/s-afadin is a dual residency protein and localizes to a novel subnuclear compartment

The AF6/afadin protein is a component of cell membranes at specialized sites of cell–cell contact. Two main splice variants exist, known as l‐ and s‐afadin, respectively. L‐afadin is widely expressed in cells of epithelial origin, whilst s‐afadin expression is restricted to the brain. Here we demonstrate that the short form of AF6/s‐afadin is a dual residency protein able to localize to the plasma membrane or nucleus whilst the long form of AF6, l‐afadin is unable to localize to the nucleus. AF6/s‐afadin clusters in a distinctive speckled pattern in the nucleus, but is unable to do so when cell cycle progression is inhibited at the G1/S or G2/M checkpoints. The formation of AF6/s‐afadin nuclear bodies is also sensitive to the transcriptional activity of the cell with inhibition of RNA polymerase activity abolishing AF6/s‐afadin nuclear clustering. AF6/s‐afadin nuclear bodies localize to a novel subnuclear compartment, failing to colocalize with other known nuclear bodies. Formation of the AF6/s‐afadin nuclear foci can be regulated by specific growth factor receptor mediated signaling events and by cytoplasmic tyrosine kinases, but does not correlate with tyrosine phosphorylation of AF6/s‐afadin. AF6/s‐afadin is a candidate for mediating control of cellular growth processes by regulated translocation to the nucleus. J. Cell. Physiol. 210: 212–223, 2007. © 2006 Wiley‐Liss, Inc.