The scavenger receptor expressed by endothelial cells (SREC)-I was originally identified in a human endothelial cell line by expression cloning. Subsequently it was shown that the cytoplasmic domain of SREC-I mediates the neurite-like outgrowth of murine fibroblastic L cells through interaction with advillin, a member of gelsolin/villin family of actin regulatory proteins. In this work, we further searched for a binding protein to the cytoplasmic domain of the receptor, which might be required for the morphological change of L cells and identified protein phosphatase 1 alpha (PP1 alpha) as a binding protein to this domain. It was revealed that PP1 alpha binds to the central region (i.e., residues between 461 and 560) of the cytoplasmic domain of the receptor. By the expression of truncated forms of SREC-I lacking G terminal amino acids, it was suggested that the morphological change is a two step process (i.e., elongation/sprouting and process formation) mediated by two distinctive cytoplasmic regions of SREC-I and PP1 alpha is required for the process formation. Our system may be useful for the elucidation of the mechanism of morphological maturation of neuronal cells such as dorsal root ganglion neurons that express SREC-I during early development. (c) 2007 Elsevier Inc. All rights reserved.