Our lab is interested in understanding the fundamentals of centrosome biogenesis.
We aim to uncovering the mechanisms that control the centriole duplication and centrosome maturation cycles. Through our own genome-wide RNAi screen and from other published screens, we now have a large number of candidate genes that play critical roles in these two cycles. What is lacking in the field is a true understanding of these proteins functions. Our lab uses a variety of biochemical and cell biological methods, including high resolution live cell imaging, to perform structure/function studies on known and candidate centrosomal proteins. One such protein we are currently investigating is the human Pericentrin ortholog, termed Pericentrin-Like-Protein in Drosophila. Our in-vivo structure/function analysis of PLP has revealed many new functional aspects of this protein, which are most likely conserved from Drosophila to Humans. Similar experiments are being carried out on a group of proteins that have been shown to preferentially localize to either the mother or the daughter centriole. In support of this project, we have generated many molecular tools and transgenic animals that will be used to perform standard cell biological experimentation in combination with genetic loss-of-function analysis using RNAi in cell culture and allelic analysis in the animal.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2012
Total Cost
$711,377
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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Varadarajan, Ramya; Rusan, Nasser M (2018) Bridging centrioles and PCM in proper space and time. Essays Biochem 62:793-801
Citron, Y Rose; Fagerstrom, Carey J; Keszthelyi, Bettina et al. (2018) The centrosomin CM2 domain is a multi-functional binding domain with distinct cell cycle roles. PLoS One 13:e0190530
McLamarrah, Tiffany A; Buster, Daniel W; Galletta, Brian J et al. (2018) An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly. J Cell Biol 217:1217-1231
Beach, Jordan R; Bruun, Kyle S; Shao, Lin et al. (2017) Actin dynamics and competition for myosin monomer govern the sequential amplification of myosin filaments. Nat Cell Biol 19:85-93
Galletta, Brian J; Fagerstrom, Carey J; Schoborg, Todd A et al. (2016) A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4. Nat Commun 7:12476
Galletta, Brian J; Jacobs, Katherine C; Fagerstrom, Carey J et al. (2016) Asterless is required for centriole length control and sperm development. J Cell Biol 213:435-50
Klebba, Joseph E; Buster, Daniel W; McLamarrah, Tiffany A et al. (2015) Autoinhibition and relief mechanism for Polo-like kinase 4. Proc Natl Acad Sci U S A 112:E657-66
Klebba, Joseph E; Galletta, Brian J; Nye, Jonathan et al. (2015) Two Polo-like kinase 4 binding domains in Asterless perform distinct roles in regulating kinase stability. J Cell Biol 208:401-14
Plevock, Karen M; Galletta, Brian J; Slep, Kevin C et al. (2015) Newly Characterized Region of CP190 Associates with Microtubules and Mediates Proper Spindle Morphology in Drosophila Stem Cells. PLoS One 10:e0144174
Galletta, Brian J; Rusan, Nasser M (2015) A yeast two-hybrid approach for probing protein-protein interactions at the centrosome. Methods Cell Biol 129:251-277

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