Regulation of microtubule organizing centers (MTOCs) contributes to the reorganization of the microtubule cytoskeleton during the cell cycle and in development. Fission yeast Schizosaccharomyces pombe cells use three types of MTOCs for building different microtubule structures through the cell cycle. During interphase, microtubule bundles are organized by multiple interphase microtubule organizing centers (iMTOCs) on the nuclear envelope. iMTOCs are required for nuclear positioning and may contain proteins involved in microtubule nucleation, bundling and attachment to the nuclear envelope. Establishment of iMTOCs occurs during cytokinesis, concurrent with the disassembly of the equatorial MTOC (eMTOC) located at the cell division site. Here, we will determine mechanisms that orchestrate the breakdown of the eMTOC and the formation of iMTOCs.
Our specific aims are: 1) to determine the roles of a J-domain protein rsp1p and an MTOC protein coi1p in regulation of Emtoc disassembly. 2) To determine the function of motile particles (satellites) containing MTOC components. We will test a model that satellites transport MTOC components from the disassemblying eMTOC to the nuclear envelope, where they contribute to iMTOC formation. 3) To identify nuclear envelope proteins that attaches iMTOCs and interphase MT bundles to the outer nuclear envelope for nuclear positioning. This work will provide insights into the regulation of microtubules of many cell types such as epithelial and muscle cells. As centrosomal defects are prevalent in cancer, MTOC regulation is now an important area in cancer research.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM069670-03
Application #
7173421
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Deatherage, James F
Project Start
2005-02-01
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$271,441
Indirect Cost
Name
Columbia University (N.Y.)
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Chang, Fred; Atilgan, Erdinc; Burgess, David et al. (2014) Manipulating cell shape by placing cells into micro-fabricated chambers. Methods Mol Biol 1136:281-90
Al-Bassam, Jawdat; Kim, Hwajin; Flor-Parra, Ignacio et al. (2012) Fission yeast Alp14 is a dose-dependent plus end-tracking microtubule polymerase. Mol Biol Cell 23:2878-90
Hou, Haitong; Zhou, Zhou; Wang, Yu et al. (2012) Csi1 links centromeres to the nuclear envelope for centromere clustering. J Cell Biol 199:735-44
Atilgan, Erdinc; Burgess, David; Chang, Fred (2012) Localization of cytokinesis factors to the future cell division site by microtubule-dependent transport. Cytoskeleton (Hoboken) 69:973-82
Basu, Roshni; Chang, Fred (2011) Characterization of dip1p reveals a switch in Arp2/3-dependent actin assembly for fission yeast endocytosis. Curr Biol 21:905-16
Minc, Nicolas; Burgess, David; Chang, Fred (2011) Influence of cell geometry on division-plane positioning. Cell 144:414-26
Al-Bassam, Jawdat; Kim, Hwajin; Brouhard, Gary et al. (2010) CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule. Dev Cell 19:245-58
Bathe, Mark; Chang, Fred (2010) Cytokinesis and the contractile ring in fission yeast: towards a systems-level understanding. Trends Microbiol 18:38-45
Chang, Fred; Martin, Sophie G (2009) Shaping fission yeast with microtubules. Cold Spring Harb Perspect Biol 1:a001347
Minc, Nicolas; Bratman, Scott V; Basu, Roshni et al. (2009) Establishing new sites of polarization by microtubules. Curr Biol 19:83-94

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