Cytokinesis is a process that occurs at the end of each mitotic cycle in which an actin-based structure known as the contractile ring, constricts the plasma membrane and divides the cytoplasm into two compartments. Despite it central importance, remarkably little is known about many aspects of this process. Unresolved issues include the signals that control the timing and position of the contractile ring, the mechanisms by which actin and other components are recruited to the contractile ring, and the manner in which mitosis and cytokines are coordinated. In addition, it is likely that many components of the contractile ring have not been identified. The metaphase furrows which form during the cortical divisions of the syncytial Drosophila embryo provide a model system in which to study cytokinesis. These transient actin-myosin based furrows ar analogous to the contractile rings of conventional dividing cells. As many components are conserved in the two structures, lessons learned from one system are likely to apply to the other. This system is amenable to molecular, genetic, biochemical, and cellular approaches. A growing collection of mutations (currently there are 7) identifies genes that are specifically required for metaphase furrow formation. This proposal primarily focuses on two of these genes, nuclear-fallout (nuf) and grapes (grp). nuf encodes a protein with extensive coiled coil domains and preliminary analysis indicates that it is required for the assembly of actin and myosin in the furrows. grp encodes is a serine-threonine kinase, and preliminary analysis indicates it is required for the assembly of myosin in the metaphase furrows. Our goals are to precisely define the in vivo functions of these proteins in the formation of the metaphase furrows and to elucidate the mechanisms by which they are carried out. In addition, this collection of 7 mutations provides a unique opportunity to analyze how the vents of metaphase furrow formation are coordinated.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM046409-09S1
Application #
6445339
Study Section
Genetics Study Section (GEN)
Program Officer
Deatherage, James F
Project Start
1991-08-01
Project End
2001-12-31
Budget Start
2001-05-01
Budget End
2001-12-31
Support Year
9
Fiscal Year
2001
Total Cost
$57,426
Indirect Cost
Name
University of California Santa Cruz
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Santa Cruz
State
CA
Country
United States
Zip Code
95064
Brose, Lotti; Crest, Justin; Tao, Li et al. (2017) Polo kinase mediates the phosphorylation and cellular localization of Nuf/FIP3, a Rab11 effector. Mol Biol Cell 28:1435-1443
Tao, Li; Fasulo, Barbara; Warecki, Brandt et al. (2016) Tum/RacGAP functions as a switch activating the Pav/kinesin-6 motor. Nat Commun 7:11182
DeBruhl, Heather; Albertson, Roger; Swider, Zachary et al. (2016) Rop, the Sec1/Munc18 homolog in Drosophila, is required for furrow ingression and stable cell shape during cytokinesis. J Cell Sci 129:430-43
Oliveira, Raquel A; Kotadia, Shaila; Tavares, Alexandra et al. (2014) Centromere-independent accumulation of cohesin at ectopic heterochromatin sites induces chromosome stretching during anaphase. PLoS Biol 12:e1001962
Martins, T; Kotadia, S; Malmanche, N et al. (2013) Strategies for outcrossing and genetic manipulation of Drosophila compound autosome stocks. G3 (Bethesda) 3:1-4
Kotadia, Shaila; Montembault, Emilie; Sullivan, William et al. (2012) Cell elongation is an adaptive response for clearing long chromatid arms from the cleavage plane. J Cell Biol 199:745-53
Crest, Justin; Concha-Moore, Kirsten; Sullivan, William (2012) RhoGEF and positioning of rappaport-like furrows in the early Drosophila embryo. Curr Biol 22:2037-41
Azucena, Oscar; Crest, Justin; Kotadia, Shaila et al. (2011) Adaptive optics wide-field microscopy using direct wavefront sensing. Opt Lett 36:825-7
Royou, Anne; Gagou, Mary E; Karess, Roger et al. (2010) BubR1- and Polo-coated DNA tethers facilitate poleward segregation of acentric chromatids. Cell 140:235-45
Azucena, Oscar; Crest, Justin; Cao, Jian et al. (2010) Wavefront aberration measurements and corrections through thick tissue using fluorescent microsphere reference beacons. Opt Express 18:17521-32

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