A Genetic Approach to Study the Role of Nuclear Envelope Components in Nuclear Positioning

Starr, Daniel A.; Han, Min

doi:10.1002/0470093765.ch14

Cited by 25 publications

(12 citation statements)

References 5 publications

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“…P-cell nuclear migration in C. elegans is an excellent model in which to study nuclear movements through constrictions for the following reasons. (1) Nuclear migration can be genetically separated from cell migration (Starr and Han, 2005). (2) Pcell nuclei undergo significant morphological changes (Fig.…”

Section: Discussionmentioning

confidence: 99%

Nuclei migrate through constricted spaces using microtubule motors and actin networks in C. elegans hypodermal cells

et al. 2016

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Cellular migrations through constricted spaces are a crucial aspect of many developmental and disease processes including hematopoiesis, inflammation and metastasis. A limiting factor in these events is nuclear deformation. Here, we establish an in vivo model in which nuclei can be visualized while moving through constrictions and use it to elucidate mechanisms for nuclear migration. C. elegans hypodermal P-cell larval nuclei traverse a narrow space that is about 5% their width. This constriction is blocked by fibrous organelles, structures that pass through P cells to connect the muscles to cuticle. Fibrous organelles are removed just prior to nuclear migration, when nuclei and lamins undergo extreme morphological changes to squeeze through the space. Both actin and microtubule networks are organized to mediate nuclear migration. The LINC complex, consisting of the SUN protein UNC-84 and the KASH protein UNC-83, recruits dynein and kinesin-1 to the nuclear surface. Both motors function in P-cell nuclear migration, but dynein, functioning through UNC-83, plays a more central role as nuclei migrate towards minus ends of polarized microtubule networks. Thus, the nucleoskeleton and cytoskeleton are coordinated to move nuclei through constricted spaces.

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Section: Discussionmentioning

confidence: 99%

Nuclei migrate through constricted spaces using microtubule motors and actin networks in C. elegans hypodermal cells

et al. 2016

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“…Our current understanding of the molecular mechanisms of the SUN-KASH nuclear-envelope bridge is based on characterizations of genetic mutants in Caenorhabditis elegans and Drosophila with mispositioned nuclei (reviewed in Starr & Fischer 2005, Starr & Han 2005, Wilhelmsen et al 2006). SUN proteins were discovered by molecular analysis of C. elegans unc-84 .…”

Section: Discovery Of Kash and Sun Proteins And The Formation Of The mentioning

confidence: 99%

Interactions Between Nuclei and the Cytoskeleton Are Mediated by SUN-KASH Nuclear-Envelope Bridges

Starr

Fridolfsson

2010

Annu. Rev. Cell Dev. Biol.

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The nuclear envelope links the cytoskeleton to structural components of the nucleus. It functions to coordinate nuclear migration and anchorage, organize chromatin, and aid meiotic chromosome pairing. Forces generated by the cytoskeleton are transferred across the nuclear envelope to the nuclear lamina through a nuclear-envelope bridge consisting of SUN (Sad1 and UNC-84) and KASH (Klarsicht, ANC-1 and Syne/Nesprin homology) proteins. Some KASH-SUN combinations connect microtubules, centrosomes, actin filaments, or intermediate filaments to the surface of the nucleus. Other combinations are used in cell cycle control, nuclear import, or apoptosis. Interactions between the cytoskeleton and the nucleus also affect global cytoskeleton organization. SUN and KASH proteins were identified through genetic screens for mispositioned nuclei in model organisms. Knockouts of SUN or KASH proteins disrupt neurological and muscular development in mice. Defects in SUN and KASH proteins have been linked to human diseases including muscular dystrophy, ataxia, progeria, lissencephaly, and cancer.

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“…5,6 ). Mutations in unc-83 or unc-84 disrupt nuclear migration events in at least three tissues 7-9 while mutations in anc-1 or unc-84 disrupt nuclear anchorage in a wide variety of cells.…”

Section: Kash and Sun Proteins Bridge The Nuclear Envelopementioning

confidence: 99%

Communication between the cytoskeleton and the nuclear envelope to position the nucleus

Starr

2007

Mol. BioSyst.

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In most eukaryotic cells, the nucleus is localized to a specific location. This highlight article focuses on recent advances describing the mechanisms of nuclear migration and anchorage. Central to nuclear positioning mechanisms is the communication between the nuclear envelope and the cytoskeleton. All three components of the cytoskeleton-microtubules, actin filaments and intermediate filaments -are involved in nuclear positioning to varying degrees in different cell types. KASH proteins on the outer nuclear membrane connect to SUN proteins on the inner nuclear membrane. Together they transfer forces between the cytoskeleton and the nuclear lamina. Once at the outer nuclear membrane, KASH proteins can interact with the cytoskeleton. Nuclear migrations are a component of many cellular migration events and defects in nuclear positioning lead to human diseases, most notably lissencephaly.

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A Genetic Approach to Study the Role of Nuclear Envelope Components in Nuclear Positioning

Cited by 25 publications

References 5 publications

Nuclei migrate through constricted spaces using microtubule motors and actin networks in C. elegans hypodermal cells

Nuclei migrate through constricted spaces using microtubule motors and actin networks in C. elegans hypodermal cells

Interactions Between Nuclei and the Cytoskeleton Are Mediated by SUN-KASH Nuclear-Envelope Bridges

Communication between the cytoskeleton and the nuclear envelope to position the nucleus

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