NCAM140 is translocated into the nucleus by an importin-β1-dependent mechanism

The neural cell adhesion molecule (NCAM) is important for neural development and for plasticity in adult brain. Previous studies demonstrated a calmodulin-dependent import of a transmembrane fragment of NCAM into the nucleus that regulates gene expression. In a protein macroarray we identified importin-β1 as a potential interaction partner of NCAM's cytoplasmic tail. The interaction was verified and an importin-β1-dependent import of NCAM into the nucleus could be demonstrated using quantitative immunofluorescence analysis. Generation of NCAM deletion mutants revealed that the last amino acids of the cytoplasmic region of NCAM are dispensable whereas other parts of NCAM's cytoplasmic tail take part in its nuclear translocation. With this study we propose an alternative nuclear route for NCAM via the classical importin-mediated import.