Matefin, a Caenorhabditis elegans germ line-specific SUN-domain nuclear membrane protein, is essential for early embryonic and germ cell development

Abstract

Caenorhabditis elegans mtf-1 encodes matefin, which has a predicted SUN domain, a coiled-coil region, an anti-erbB-2 IgG domain, and two hydrophobic regions. We show that matefin is a nuclear membrane protein that colocalizes in vivo with Ce-lamin, the single nuclear lamin protein in C. elegans, and binds Ce-lamin in vitro but does not require Ce-lamin for its localization. Matefin is detected in all embryonic cells until midembryogenesis and thereafter only in germ-line cells. Embryonic matefin is maternally deposited, and matefin is the first nuclear membrane protein known to have germ line-restricted expression. Animals homozygous for an mtf-1 deletion allele show that matefin is essential for germ line maturation and survival. However, matefin is also required for embryogenesis because mtf-1 (RNAi) embryos die around the Ϸ300-cell stage with defects in nuclear structure, DNA content, and chromatin morphology. Down-regulating matefin in mes-3 animals only slightly enhances embryonic lethality, and elimination of UNC-84, the only other SUN-domain gene in C. elegans, has no affect on mtf-1 (RNAi) animals. Thus, mtf-1 mediates a previously uncharacterized pathway(s) required for embryogenesis as well as germ line proliferation or survival. Lamins are nuclear intermediate filament proteins found in metazoan cells at the nuclear periphery and in the nucleoplasm (1). Lamins interact with most known inner nuclear membrane proteins as well as with several nucleoplasmic proteins (2). Nuclear architecture, cell cycle progression, DNA replication, and RNA transcription and splicing all depend on lamins (3, 4). Consistent with such roles, many of these laminbinding proteins also bind transcription repressors and chromatin proteins.To understand nuclear lamins and lamin-associated protein functions in vivo we turned to Caenorhabditis elegans, studying its single lamin protein, Ce-lamin (5), and three inner nuclear membrane proteins, Ce-emerin, Ce-MAN1 (5, 6), and UNC-84 (7). UNC-84 contains an Ϸ120-residue SUN (Sad1p-UNC-84 homology) domain (8) with an unknown function. The SUN domain is also found in four human proteins, two of which localize at the nuclear envelope (9). UNC-84 is expressed in most C. elegans cells, and it depends on Ce-lamin for its nuclearenvelope localization (7). However, mutations in unc-84 cause nuclear migration or nuclear anchoring defects in only a subset of cells, leading to uncoordinated movement (8). At least two nuclear-envelope proteins, UNC-83 and ANC-1, require the SUN domain of UNC-84 for their nuclear-envelope localization and ability to regulate nuclear position (10). To explain their nuclear-envelope anchoring, a ''bridging model'' was proposed in which the transmembrane domains of UNC-83 and ANC-1 cross the outer nuclear membrane (ONM), and their luminal domains interact with the luminal domain of UNC-84 embedded in the inner nuclear membrane (7, 10).Based on the hypothesis that the SUN domain defined a new family of nuclear-envelope proteins, we searched the C. elegans genome for ot...

MPS3 mediates meiotic bouquet formation in Saccharomyces cerevisiae

“…Anc-1, in turn, interacts with the actin cytoskeleton to anchor the nucleus. A similar model has been elaborated for the role of a second C. elegans SUN domain protein, Sun1/Matefin, in mediating interaction of the nucleus with the centrosome (29,33), and the mammalian Sun1 and Sun2 proteins also are implicated in bridging the nuclear envelope (54,55). A role for the actin cytoskeleton in bouquet formation is suggested by the cessation of telomere clustering during meiotic prophase in S. cerevisiae after addition of latrunculin, which depolymerizes actin filaments (14).…”

“…SUN domain proteins are present in eukaryotes from fungi to vertebrates, and SUN domains are proposed to be protein interaction domains (28,29,31,32,35,51,52). Unc-84, an inner nuclear membrane protein, is proposed to bridge the perinuclear space to interact with a second protein, Anc-1, of the outer nuclear envelope (32,37,53).…”

“…The present study demonstrates a critical requirement for the Ndj1p-Mps3p interaction for bouquet formation in budding yeast. Mps3p is a member of the SUN family of proteins which have been identified in the nuclear envelope of yeasts, worms and mammals, and have been implicated in bridging the nuclear envelope to connect the nuclear contents with the cytoskeleton in mitosis and in meiosis (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Identification of Mps3p as a conserved component of the machinery that moves chromosomes in meiotic prophase will lead to further components of the machinery and to new, testable models for the regulation and function of these movements.…”

SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice

“…Similarly, in flies, the SUN protein Klaroid is required for the localization of KASH protein Klarsicht to the NE and for nuclear migration in the eye (15). Genetic studies in the worm and yeast also have indicated roles of SUN proteins in mediating the interactions between the NE and centrosome, centromeres, and telomeres at various stages of mitotic and meiotic cells (16)(17)(18)(19)(20)(21)(22).Mammalian SUN1 and SUN2 proteins were first identified as homologues of C. elegans UNC-84 (10). SUN1 and SUN2 are broadly distributed in mouse tissues, whereas 2 other, more recently identified SUN proteins, SUN3 and SPAG4, appear to be expressed in a limited amount of tissues (4,(23)(24)(25).…”

“…Similarly, in flies, the SUN protein Klaroid is required for the localization of KASH protein Klarsicht to the NE and for nuclear migration in the eye (15). Genetic studies in the worm and yeast also have indicated roles of SUN proteins in mediating the interactions between the NE and centrosome, centromeres, and telomeres at various stages of mitotic and meiotic cells (16)(17)(18)(19)(20)(21)(22).…”