Nuclear and mitochondrial inheritance in yeast depends on novel cytoplasmic structures defined by the MDM1 protein.

McConnell, Stephen J.; Yaffe, Michael P.

doi:10.1083/jcb.118.2.385

Cited by 95 publications

(72 citation statements)

References 53 publications

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“…The high affinity Vam7p PX domain comprises the N-terminal half of a 317-amino acid protein, and in vivo studies of deletion mutants indicate that it is sufficient for targeting Vam7p to the yeast vacuole, where it acts as a t-SNARE (3). The remaining yeast protein with a high affinity PX domain is Mdm1p, a 51-kDa protein that functions in nuclear and mitochondrial inheritance and localizes to punctate structures that are distributed throughout the yeast cytoplasm (22). Although not previously implicated in Mdm1p function, our finding that PtdIns-3-P binds strongly and specifically to the Mdm1p PX domain plus a report that several mutations in the Mdm1p PX domain affect nuclear and/or mitochondrial inheritance (23) suggest an important role for PtdIns-3-P binding in Mdm1p action.…”

Section: Fig 2 Sds-page Analysis Of Gst-px Fusion Proteinsmentioning

confidence: 99%

All Phox Homology (PX) Domains from Saccharomyces cerevisiae Specifically Recognize Phosphatidylinositol 3-Phosphate

Lemmon

2001

Journal of Biological Chemistry

196

183

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Phox homology (PX) domains are named for a 130-amino acid region of homology shared with part of two components of the phagocyte NADPH oxidase (phox) complex. They are found in proteins involved in vesicular trafficking, protein sorting, and lipid modification. It was recently reported that certain PX domains specifically recognize phosphatidylinositol 3-phosphate (PtdIns-3-P) and drive recruitment of their host proteins to the cytoplasmic leaflet of endosomal and/or vacuolar membranes where this phosphoinositide is enriched. We have analyzed phosphoinositide binding by all 15 PX domains encoded by the Saccharomyces cerevisiae genome. All yeast PX domains specifically recognize PtdIns-3-P in protein-lipid overlay experiments, with just one exception (a significant sequence outlier). In surface plasmon resonance studies, four of the yeast PX domains bind PtdIns-3-P with high (micromolar range) affinity. Although the remaining PX domains specifically recognize PtdIns-3-P, they bind this lipid with only low affinity. Interestingly, many proteins with "low affinity" PX domains are known to form large multimeric complexes, which may increase the overall avidity for membranes. Our results establish that PtdIns-3-P, and not other phosphoinositides, is the target of all PX domains in S. cerevisiae and suggest a role for PX domains in assembly of multiprotein complexes at specific membrane surfaces.The phox homology (PX) 1 domain (1) was first identified in 1996 as a 130-amino acid region of homology present in two components (p40 phox and p47 phox ) of the phagocyte NADPH oxidase (phox) complex plus a wide variety of other proteins with diverse functions. Many PX domain-containing proteins are involved in vesicular trafficking, protein sorting, and lipid modification. The presence of a central PXXP motif in most (but not all) PX domains stimulated the initial suggestion that they represent binding partners for SH3 domains (1) and therefore may direct inter-and/or intramolecular protein-protein interactions. In support of this, the PX domain from p47 phox was recently shown to interact, albeit weakly, with the C-terminal SH3 domain from the same protein (2).A different class of PX domain ligand was recently reported by several groups who described binding of PX domains to phosphoinositides. Specifically, the PX domains from the yeast vacuolar t-SNARE Vam7p (3, 4), sorting nexin-3 (SNX3) (5), and p40 phox (6, 7) were all shown to bind selectively to phosphatidylinositol 3-phosphate (PtdIns-3-P), which is enriched in endosomal and vacuolar membranes (8). Isolated PX domains from p40 phox and SNX3 were found to be independently capable of localizing to endosomal structures in vivo in a manner that depends upon their ability to bind PtdIns-3-P and on PI-3-kinase activity (5-7). Similarly, analysis of deletion mutants indicated that the Vam7p PX domain is sufficient for localization of that protein to vacuoles and endosomes in yeast (3). Other phosphoinositides have been reported as the preferred ligands for certain PX domain...

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Section: Fig 2 Sds-page Analysis Of Gst-px Fusion Proteinsmentioning

confidence: 99%

All Phox Homology (PX) Domains from Saccharomyces cerevisiae Specifically Recognize Phosphatidylinositol 3-Phosphate

Lemmon

2001

Journal of Biological Chemistry

196

183

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“…Other mutants have been identified that also exhibit a nuclear migration defect (Watts et al, 1987;Berlin et al, 1990;Kormanec et al, 1991;Ursic and Culbertson, 1991;McConnell and Yaffe, 1992). The specific role of these genes in nuclear migration is not known and in all cases except numl the nuclear migration defect is only one trait of a more complex phenotype.…”

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The JNM1 gene in the yeast Saccharomyces cerevisiae is required for nuclear migration and spindle orientation during the mitotic cell cycle.

McMillan

Tatchell

1994

The Journal of Cell Biology

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Abstract. JNM1, a novel gene on chromosome XIII in the yeast Saccharomyces cerevisiae, is required for proper nuclear migration, jnml null mutants have a temperature-dependent defect in nuclear migration and an accompanying alteration in astral microtubules. At 30°C, a significant proportion of the mitotic spindles is not properly located at the neck between the mother cell and the bud. This defect is more severe at low temperature. At ll°C, 60% of the cells accumulate with large buds, most of which have two DAPI staining regions in the mother cell. Although mitosis is delayed and nuclear migration is defective in jnml mutants, we rarely observe more than two nuclei in a cell, nor do we frequently observe anuclear cells. No loss of viability is observed at ll°C and cells continue to grow exponentially with increased doubling time. T HE nuclei in the budding yeast Saccharomyces cerevisiae migrate to the neck between the mother cell and the bud prior to mitosis and the spindle microtubules orient along the long axis of the cell. At mitosis the spindle elongates through the neck between the mother cell and the bud and chromosomes separate, depositing one set of chromosomes in the mother cell body and one set in the bud. A key role for microtubules in this process has been shown by the inhibitory effects on nuclear migration by microtubule inhibitors (Jacobs et al., 1988) and by defects in nuclear migration exhibited by some B tubulin mutants (Huffaker et al., 1988). Cytoplasmic (or astral) microtubules appear to be mainly responsible for nuclear migration.Mutant alleles of the tub2 gene that impart a specific defect in astral microtubule stability show defects in nuclear migration during mitosis or karyogamy, but have relatively little

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“…This inheritance requires the growth and division of preexisting mitochondria and the distribution of mitochondria between daughter cells before cell division (Attardi and Schatz, 1988). Cytoskeletal elements have been implicated in the positioning and movement of mitochondria (Heggeness et al, 1978;Chen, 1988;McConnell and Yaffe, 1992;Drubin et al, 1993), but mechanisms underlying mitochondrial inheritance are poorly understood.Mitochondria are usually found as snakelike tubules, widely distributed in the eukaryotic cytoplasm (Tzagoloff, 1982;Bereiter-Hahn, 1990). Often, these tubules are interconnected into extended mitochondrial reticula (Stevens, 1981;Chen, 1988).…”

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confidence: 99%

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confidence: 99%

Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane.

Sogo

Yaffe

1994

The Journal of Cell Biology

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Abstract. Yeast cells with the mdm/0 mutation possess giant spherical mitochondria and are defective for mitochondrial inheritance. The giant mitochondria display classical features of mitochondrial ultrastructure, yet they appear incapable of movement or division. Genetic analysis indicated that the mutant phenotypes resulted from a single nuclear mutation, and the isolated MDMIO gene restored wild-type mitochondrial distribution and morphology when introduced into mutant cells. MDMIO encodes a protein of 56.2 kD located in the mitochondrial outer membrane. Depletion of Mdml0p from cells led to a condensation of normally extended, tubular mitochondria into giant spheres, and reexpression of the protein resulted in a rapid restoration of normal mitochondrial morphology. These results demonstrate that Mdml0p can control mitochondrial morphology, and that it plays a role in the inheritance of mitochondria. MITOCHONDRIAL inheritance is an essential component of cell proliferation (Yaffe, 1991b). This inheritance requires the growth and division of preexisting mitochondria and the distribution of mitochondria between daughter cells before cell division (Attardi and Schatz, 1988). Cytoskeletal elements have been implicated in the positioning and movement of mitochondria (Heggeness et al., 1978;Chen, 1988;McConnell and Yaffe, 1992;Drubin et al., 1993), but mechanisms underlying mitochondrial inheritance are poorly understood.Mitochondria are usually found as snakelike tubules, widely distributed in the eukaryotic cytoplasm (Tzagoloff, 1982;Bereiter-Hahn, 1990). Often, these tubules are interconnected into extended mitochondrial reticula (Stevens, 1981;Chen, 1988). Microscopic studies of live cells have revealed that these mitochondrial networks are extremely dynamic, with tubular processes undergoing frequent fragmentation, branching, and fusion, as well as redistribution within the cytoplasm (Bereiter-Hahn, 1990; Koning et ai., 1993). In addition to the dynamic properties of mitochondria found in most types of cells, certain pathological conditions lead to gross changes in mitochondrial morphology, including the development of giant mitochondria (Tandler and Hoppel, 1986;Inagaki et al., 1992). The molecular bases for these changes in mitochondrial morphology and distribution in both normal and diseased cells are unknown.We recently described several Saccharomyces cerevisiae mutants defective for mitochondrial inheritance (McConnell et al., 1990). These mitochondrial distribution and morphology (mdm) I mutants were identified by screening collections of temperature-sensitive strains by fluorescence microscopy for cells that failed to transfer mitochondria into daughter buds during incubation at the nonpermissive temperature. Analysis of two of these mutant strains led to the identification of a novel cytoskeletal component that mediates mitochondrial inheritance Yaffe, 1992, 1993), and it indicated a role for unsaturated fatty acids in mitochondrial movement (Stewart and Yaffe, 1991). Here, we describe a new mdm m...

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Nuclear and mitochondrial inheritance in yeast depends on novel cytoplasmic structures defined by the MDM1 protein.

Cited by 95 publications

References 53 publications

All Phox Homology (PX) Domains from Saccharomyces cerevisiae Specifically Recognize Phosphatidylinositol 3-Phosphate

All Phox Homology (PX) Domains from Saccharomyces cerevisiae Specifically Recognize Phosphatidylinositol 3-Phosphate

The JNM1 gene in the yeast Saccharomyces cerevisiae is required for nuclear migration and spindle orientation during the mitotic cell cycle.

Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane.

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