title: Type F scavenger receptor SREC-I interacts with advillin, a member of the gelsolin/villin family, and induces neurite-like outgrowth.
abstract: The scavenger receptor expressed by endothelial cells (SREC) was isolated from a human endothelial cell line and consists of two isoforms named SREC-I and -II. Both isoforms have no significant homology to other types of scavenger receptors. They contain 10 repeats of epidermal growth factor-like cysteine-rich motifs in the extracellular domains and have unusually long C-terminal cytoplasmic domains with Ser/Pro-rich regions. The extracellular domain of SREC-I binds modified low density lipoprotein and mediates a homophilic SREC-I/SREC-I or heterophilic SREC-I/SREC-II trans-interaction. However, the significance of large Ser/Pro-rich cytoplasmic domains of SRECs is not clear. Here, we found that when SREC-I was overexpressed in murine fibroblastic L cells, neurite-like outgrowth was induced, indicating that the receptor can lead to changes in cell morphology. The SREC-I-mediated morphological change required the cytoplasmic domain of the protein, and we identified advillin, a member of the gelsolin/villin family of actin regulatory proteins, as a protein binding to this domain. Reduction of advillin expression in L cells by RNAi led to the absence of the described SREC-I-induced morphological changes, indicating that advillin is a prerequisite for the change. Finally, we demonstrated that SREC-I and advillin were co-expressed and interacted with each other in dorsal root ganglion neurons during embryonic development and that overexpression of both SREC-I and advillin in cultured Neuro-2a cells induced long process formation. These results suggest that the interaction of SREC-I and advillin are involved in the development of dorsal root ganglion neurons by inducing the described morphological changes.
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Shibata
authors.forename: Junko
authors.initials: J
authors.lastname: Ishii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koizumi
authors.forename: Norihito
authors.initials: N
authors.lastname: Shibata
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Koji
authors.initials: K
authors.lastname: Takio
authors.forename: Hideki
authors.initials: H
authors.lastname: Adachi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D018260:Gelsolin / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D051128:Scavenger Receptors, Class F; D014162:Transfection
chemical_list: C113762:Avil protein, mouse; D015815:Cell Adhesion Molecules; D018260:Gelsolin; D008840:Microfilament Proteins; D011973:Receptors, LDL; D051116:Receptors, Scavenger; D051128:Scavenger Receptors, Class F