Multiple mechanisms actively target the SUN protein UNC-84 to the inner nuclear membrane

• Published in: Molecular biology of the cell Vol. 22; no. 10; pp. 1739 - 1752
• Main Authors: Tapley, Erin C, Ly, Nina, Starr, Daniel A
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 15.05.2011
• Subjects: Amino Acid Sequence; Animals; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Nucleus - metabolism; Cloning, Molecular; Hydrophobic and Hydrophilic Interactions; Larva - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mutagenesis, Site-Directed; Nuclear Envelope - genetics; Nuclear Envelope - metabolism; Nuclear Localization Signals - genetics; Nuclear Localization Signals - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Peptide Fragments - metabolism; Protein Structure, Tertiary; Protein Transport - genetics; Recombinant Fusion Proteins - metabolism; Sequence Deletion
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E10-08-0733

Approximately 100 proteins are targeted to the inner nuclear membrane (INM), where they regulate chromatin and nuclear dynamics. The mechanisms underlying trafficking to the INM are poorly understood. The Caenorhabditis elegans SUN protein UNC-84 is an excellent model to investigate such mechanisms. UNC-84 recruits KASH proteins to the outer nuclear membrane to bridge the nuclear envelope (NE), mediating nuclear positioning. UNC-84 has four targeting sequences: two classical nuclear localization signals, an INM sorting motif, and a signal conserved in mammalian Sun1, the SUN--nuclear envelope localization signal. Mutations in some signals disrupt the timing of UNC-84 nuclear envelope localization, showing that diffusion is not sufficient to move all UNC-84 to the NE. Thus targeting UNC-84 requires an initial step that actively transports UNC-84 from the peripheral endoplasmic reticulum to the NE. Only when all four signals are simultaneously disrupted does UNC-84 completely fail to localize and to function in nuclear migration, meaning that at least three signals function, in part, redundantly to ensure proper targeting of UNC-84. Multiple mechanisms might also be used to target other proteins to the INM, thereby ensuring their proper and timely localization for essential cellular and developmental functions.