title: The CaaX motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope.
abstract: While the nuclear lamin proteins (A, B, and C) assemble specifically at the surface of the nuclear membrane, their sequences do not reveal stretches of hydrophobic amino acids that might explain their association with the nuclear membranes. However, the A and B lamin proteins possess Ras-like C-terminal CaaX sequence motifs, which in Ras proteins are sites of hydrophobic modifications required for membrane association and function. From the analysis of single and double lamin A mutants affecting the CaaX motif, the nuclear localization signal, and higher-order assembly properties, we propose that the CaaX motif functions as a nonspecific, low affinity membrane probe for proteins ultimately segregated to specific cellular membrane systems. Committed association with specific membranes requires additional interactions with membrane-resident factors.
authors.affiliation: Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: D
authors.initials: D
authors.lastname: Holtz
authors.forename: R A
authors.initials: RA
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Hartwig
authors.forename: F
authors.initials: F
authors.lastname: McKeon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003062:Codon / Q000235:genetics; D004251:DNA Transposable Elements; D005455:Fluorescent Antibody Technique; D006801:Humans; D034904:Lamin Type A; D034882:Lamins; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010957:Plasmids; D011487:Protein Conformation; D015398:Signal Transduction; D014162:Transfection
chemical_list: D003062:Codon; D004251:DNA Transposable Elements; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins