Characterization of two isoforms of the skeletal muscle LIM protein 1, SLIM1 - Localization of SLIM1 at focal adhesions and the isoform slimmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles inthe cytoskeleton and in nuclear-cytoplasmic communication

We have cloned and characterized a novel isoform of the skeletal muscle LIM protein 1 (SLIM1), designated SLIMMER. SLIM1 contains an N-terminal single zinc finger followed by four LIM domains. SLIMMER is identical to SLIM1 ov er the first three LIM domains but contains a novel C-terminal 96 amino aci ds with three potential bipartite nuclear localization signals, a putative nuclear export sequence, and 27 amino acids identical to the RBP-J binding region of KyoT2, a murine isoform of SLIM1. SLIM1 localized to the cytosol of So8 myoblasts and myotubes. SLIMMER was detected in the nucleus of myobl asts and, following differentiation into myotubes, was exclusively cytosoli c. Recombinant green fluorescent protein-SLIM1 localized to, the cytoplasm and associated with focal adhesions and actin filaments in COS-7 cells, whi le green fluorescent protein-SLIMMER was predominantly nuclear. SLIMMER tru ncation mutants revealed that the first nuclear localization signal mediate s nuclear localization. The addition of the proposed nuclear export sequenc e decreased the level of exclusively nuclear expression and increased cytos olic SLIMMER expression in COS-7 cells. The leucine-rich nuclear export sig nal was required for the export of SLIMMER from the nucleus of myoblasts to the cytoplasm of myotubes. Collectively, these results suggest distinct ro les for SLIM1 and SLIMMER in focal adhesions and nuclear-cytoplasmic commun ication.