Microtubules form specialized arrays with important functions in cell division, cell migration, trafficking and cell morphogenesis. Radial arrays of centrosome-anchored microtubules are typical for proliferating and migrating animal cells. However, differentiated animal cells, as well as all plant cells, can organize their microtubules without centrosomes. Although noncentrosomal microtubule arrays have been implicated in vital cellular functions, including intracellular transport and cell polarity, very little is known aboutthe mechanisms organizing microtubules in the absence of centrosomes. In the course of our preliminary studies we found that microtubule arrays in the model plant Arabidopsis thaliana are regulated by the evolutionally conserved protein phosphatase PP2A complex that includes B" regulatory subunit TON2. This proposal will elucidate the PP2A dependent molecular mechanisms of noncentrosomal microtubule array formation.
The first aim will establish the functional relationship between the PP2A dependent signaling pathway and the microtubule associate protein TON1A, which was identified in our preliminary studies as a putative TON2/PP2A effector. Functions of TON1A in microtubule nucleation and stability will be determined, and the role of TON2/PP2A signaling in regulation of the TON1A phosphorylation will be addressed. Proposed experiments will provide important insights into mechanisms regulating microtubule nucleation and stability during microtubule array formation.
The second aim of the project is to identify and characterize components of the TON1A/TON2/PP2A pathway using a sensitized genetic screen. This will set the stage for a comprehensive understanding of PP2A dependent mechanisms regulating formation of noncentrosomal microtubule arrays.

Public Health Relevance

The proposed project is aimed at understanding the mechanisms regulating the formation of the microtubule cytoskeleton. Formation of organized microtubule arrays is crucial for faithful chromosome segregation and cell differentiation, safeguarding cells against aneuploidy and cancer. The proposed study will contribute to a better understanding of human diseases caused by the dysregulation of microtubule nucleation, including human ciliary diseases and microcephaly.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15GM102839-01A1
Application #
8494947
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Gindhart, Joseph G
Project Start
2013-04-01
Project End
2016-03-31
Budget Start
2013-04-01
Budget End
2016-03-31
Support Year
1
Fiscal Year
2013
Total Cost
$288,000
Indirect Cost
$88,000
Name
Illinois State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001898142
City
Normal
State
IL
Country
United States
Zip Code
61790