Nuclear migration in Saccbaromyces cerevisiae is controlled by the highly repetitive 313 kDa NUM1 protein

Kormanec, Ján; Schaaff-Gerstenschläger, Ine; Zimmermann, Friedrich K.; Perečko, Dušan; Küntzel, Hans

doi:10.1007/bf00290678

Cited by 69 publications

(89 citation statements)

References 30 publications

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“…In a screen of the Saccharomyces cerevisiae deletion collection of nonessential genes for factors that become essential for growth on rich dextrose medium in the absence of FZO1 and DNM1, which encode the mitochondrial division and outer membrane fusion DRPs, respectively, we identified NUM1 as essential. Num1 encodes a cortical protein implicated in mitochondrial division and distribution that also functions, in nuclear migration during cell division, as an anchor for the microtubule motor dynein (12)(13)(14). We confirmed that NUM1 is essential in Δfzo1 Δdnm1 cells by tetrad analysis (Fig.…”

Section: Num1 Is Essential In δFzo1 δDnm1supporting

confidence: 76%

“…Num1 is a 313-kDa protein that contains an N-terminal coiled-coil (CC) domain, an EF hand-like motif, a region of twelve 64-aa repeats, and a C-terminal PH domain, which binds with high specificity to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] (Fig. 3A) (12,19). To gain insight into the molecular role of Num1 in mitochondria-cortex tethering, we performed structure-function analysis to test the roles of the repeat, CC, and PH regions.…”

Section: Coiled-coil and Ph Regions Of Num1 Are Required For The Cortmentioning

confidence: 99%

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Endoplasmic reticulum-associated mitochondria–cortex tether functions in the distribution and inheritance of mitochondria

Lackner

Ping

Graef

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

168

284

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To elucidate the functional roles of mitochondrial dynamics in vivo, we identified genes that become essential in cells lacking the dynamin-related proteins Fzo1 and Dnm1, which are required for mitochondrial fusion and division, respectively. The screen identified Num1, a cortical protein implicated in mitochondrial division and distribution that also functions in nuclear migration. Our data indicate that Num1, together with Mdm36, forms a physical tether that robustly anchors mitochondria to the cell cortex but plays no direct role in mitochondrial division. Our analysis indicates that Num1-dependent anchoring is essential for distribution of the static mitochondrial network in fzo1 dnm1 cells. Consistently, expression of a synthetic mitochondria-cortex tether rescues the viability of fzo1 dnm1 num1 cells. We find that the cortical endoplasmic reticulum (ER) also is a constituent of the Num1 mitochondria-cortex tether, suggesting an active role for the ER in mitochondrial positioning in cells. Thus, taken together, our findings identify Num1 as a key component of a mitochondria-ER-cortex anchor, which we termed "MECA," that functions in parallel with mitochondrial dynamics to distribute and position the essential mitochondrial network.T he shape and cellular distribution of mitochondria depend on the integrated and regulated activities of mitochondrial division and fusion, motility, and tethering (1). A key question is how these mitochondrial behaviors are coordinated to shape and position mitochondria properly in response to the changing needs of the cell. To begin to address this question, an understanding of the molecular basis of mitochondrial behaviors is essential.The molecular mechanisms underlying mitochondrial division and fusion are best understood in terms of mitochondrial behaviors (1, 2). At the heart of the molecular machines that mediate mitochondrial division and fusion are dynamin-related proteins (DRPs) that function via GTP-dependent self-assembly and GTP hydrolysismediated conformational changes to remodel membranes. The DRP Dnm1/DRP1 (in yeast and mammals, respectively) drives the scission of mitochondrial membranes, and the DRPs Fzo1/ MFN1/2 and Mgm1/OPA1 mediate fusion of the outer and inner mitochondrial membranes, respectively. The relative rates of mitochondrial division and fusion are major determinants of the steadystate structure of the organelle and greatly influence its distribution. Attenuation of mitochondrial division leads to a more interconnected, collapsed, and less distributable mitochondrial network, and attenuation of mitochondrial fusion results in mitochondrial fragmentation and pronounced defects in the transmission and distribution of mtDNA.Although mitochondrial division and fusion are important, additional parallel pathways also are likely to be important for mitochondrial distribution. For example, the stable positioning of mitochondria at specific cellular locations, an indication of active tethering mechanisms, has been observed in many different cell types. In ...

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Section: Num1 Is Essential In δFzo1 δDnm1supporting

confidence: 76%

Section: Coiled-coil and Ph Regions Of Num1 Are Required For The Cortmentioning

confidence: 99%

Endoplasmic reticulum-associated mitochondria–cortex tether functions in the distribution and inheritance of mitochondria

Lackner

Ping

Graef

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

168

284

View full text Add to dashboard Cite

show abstract

“…Num1, originally identified as a player in nuclear migration, serves to anchor dynein to the cell cortex, where dynein captures and walks along astral microtubules to help orient the mitotic spindle [1–7]. More recently, a role for Num1 in mitochondrial distribution and inheritance has been described [8–10].…”

Section: Introductionmentioning

confidence: 99%

“…Num1 is a 313 kD protein that contains an N-terminal coiled-coil (CC) domain, an EF hand-like motif, a region of twelve 64 amino acid repeats, and a C-terminal pleckstrin homology (PH) domain [1]. The CC and PH domains are critical for both of Num1’s anchoring functions.…”

Section: Introductionmentioning

confidence: 99%

The role of mitochondria in anchoring dynein to the cell cortex extends beyond clustering the anchor protein

et al. 2018

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Organelle distribution is regulated over the course of the cell cycle to ensure that each of the cells produced at the completion of division inherits a full complement of organelles. In yeast, the protein Num1 functions in the positioning and inheritance of two essential organelles, mitochondria and the nucleus. Specifically, Num1 anchors mitochondria as well as dynein to the cell cortex, and this anchoring activity is required for proper mitochondrial distribution and dynein-mediated nuclear inheritance. The assembly of Num1 into clusters at the plasma membrane is critical for both of its anchoring functions. We have previously shown that mitochondria drive the assembly of Num1 clusters and that these mitochondria-assembled Num1 clusters serve as cortical attachment sites for dynein. Here we further examine the role for mitochondria in dynein anchoring. Using a GFP-αGFP nanobody targeting system, we synthetically clustered Num1 on eisosomes to bypass the requirement for mitochondria in Num1 cluster formation. Utilizing this system, we found that mitochondria positively impact the ability of synthetically clustered Num1 to anchor dynein and support dynein function even when mitochondria are no longer required for cluster formation. Thus, the role of mitochondria in regulating dynein function extends beyond simply concentrating Num1; mitochondria likely promote an arrangement of Num1 within a cluster that is competent for dynein anchoring. This functional dependency between mitochondrial and nuclear positioning pathways likely serves as a mechanism to order and integrate major cellular organization systems over the course of the cell cycle.

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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.…”

mentioning

confidence: 99%

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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Nuclear migration in Saccbaromyces cerevisiae is controlled by the highly repetitive 313 kDa NUM1 protein

Cited by 69 publications

References 30 publications

Endoplasmic reticulum-associated mitochondria–cortex tether functions in the distribution and inheritance of mitochondria

Endoplasmic reticulum-associated mitochondria–cortex tether functions in the distribution and inheritance of mitochondria

The role of mitochondria in anchoring dynein to the cell cortex extends beyond clustering the anchor protein

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

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