By screening a yeast two-hybrid library with COOH-terminal fragments of vin
culin/metavinculin as the bait, we identified a new protein termed raver1.
Raver1 is an 80-kD multidomain protein and widely expressed but to varying
amounts in different cell lines. In situ and in vitro, raver1 forms complex
es with the microfilament-associated proteins vinculin, metavinculin, and a
lpha -actinin and colocalizes with vinculin/metavinculin and a-actinin at m
icrofilament attachment sites, such as cell-cell and cell matrix contacts o
f epithelial cells and fibroblasts, respectively, and in costameres of skel
etal muscle. The NH2-terminal part of raver1 contains three RNA recognition
motifs with homology to members of the heterogeneous nuclear RNP (hnRNP) f
amily. Raver1 colocalizes with polypyrimidine tract binding protein (PTB)/h
nRNP1, a protein involved in RNA splicing of microfilament proteins, in the
perinucleolar compartment and forms complexes with PTB/hnRNP1. Hence, rave
r1 is a dual compartment protein, which is consistent with the presence of
nuclear location signal and nuclear export sequence motifs in its sequence.
During muscle differentiation, raver1 migrates from the nucleus to the cos
tamere. We propose that raver1 may coordinate RNA processing and targeting
as required for microfilament anchoring in specific adhesion sites.