Abstract

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. In the past year we have completed a yeast-2-hybrid screen to identify the interactions between 94 centrosome proteins. We have completed the detailed analysis of 22 centrosome proteins and have identified 219 novel interactions. In addition to these core proteins, we have interaction data on 72 others. We are now focusing on understanding several critical centrosome proteins in extreme detail. One such protein is called Asterless, which is thought to be a protein scaffold at the centrosome. Our interactome has identified many Asterless binding partners, of which we are investigating three: Cep97, CP309 and Plk4. Each of these interactions is required for a unique stage within the centrosome life cycle.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006104-03
Application #
8746667
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$548,926
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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
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
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

Showing the most recent 10 out of 13 publications