Cell-cycle-dependent cell polarity control

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

↗ Live URL (may be dead)

Document text

Principal Investigator: Maitreyi  Das
Organization: BOSTON COLLEGE
Fiscal Year: 2024
Award: $296,786
Funding agency: National Institute of General Medical Sciences

PROJECT SUMMARY/ABSTRACT
Polarized cells in retain their shape in every cell cycle and this is essential to their proper function. Anomalies
in polarized cell shape can result in cancer, metabolic disorders, and loss of tissue integrity. Here, we will
investigate a long-standing question of how cells consistently regain their polarity after each round of division.
This investigation will be conducted using the fission yeast, Schizosaccharomyces pombe model system that
provides many well characterized genetic tools to manipulate conserved proteins that influence cell shape
following division. Cdc42 is the major regulator of polarized growth. In fission yeast, cells halt polarized Cdc42
activation and consequent growth at the cell ends during mitosis. After completion of division, these cell ends
resume Cdc42 activation and cell growth. After division, Cdc42 activation and polarized growth always
resumes in a monopolar manner from the old end that pre-exists from the previous generation. The cell
transitions to bipolar growth when Cdc42 activation also resumes at the newly formed cell end in the G2 phase
of the cell cycle. Our preliminary data indicate that resumption of Cdc42 activation at the old end after division
and transition to bipolar activation in G2 are cell cycle dependent. Our central hypothesis is that Cdc42 is
differentially regulated at the cell ends by distinct cell-cycle-dependent cues to establish the cell polarization
pattern. We will test this hypothesis by pursuing the following specific aims, [1] Determine how Cdc42
activation resumes at the cell ends in the G1/S phase; [2] Elucidate how a memory of growth from the previous
cell cycle enables the pre-existing old end to initiate Cdc42 activation first; [3] Explain how the transition from
monopolar to bipolar growth occur in G2 phase. With this project we expect to mechanistically understand how
Cdc42 activation and associated growth patterns are modulated in different cell cycle stages. We will examine
how signals from one cell cycle inform the growth pattern in the next generation. This will provide much needed
insights into the principles that preserve polarized cell shape in complex systems. Due to the conserved nature
of the proteins involved in this investigation, we expect that our findings will be relevant cell shape control in
higher eukaryotes and provide potential therapeutic or diagnostic targets for diseases such as cancer.

Terms: <Biologic Models><Biological Models><Body Tissues><Cancers><Cell Body><Cell Communication and Signaling><Cell Cycle><Cell Cycle Stage><Cell Division Cycle><Cell Growth and Maintenance><Cell Maintenance><Cell Polarity><Cell Shape><Cell Signaling><Cell division><Cells><Cellular Expansion><Cellular Growth><Cellular biology><Chemicals><Complex><Cues><Cyclin B><Cytokinesis><Cytoplasmic Division><Data><Development><Diagnostic><Disease><Disorder><Eukaryota><Eukaryote><Fission Yeast><G1 Arrest><G1 Block><G2 Phase><G2 period><GDP Dissociation Factor><GDP Dissociation Stimulators><GDP Exchange Factors><GDP-GTP Exchange Protein><GDP-GTP Reversing Factors><GTP GDP exchange factor><GTP Phosphohydrolases><GTPases><Gap Phase 2><Generalized Growth><Generations><Genetic><Growth><Guanine Nucleotide Exchange Factors><Guanine Nucleotide Exchange Protein><Guanine Nucleotide Releasing Factors><Guanosine Triphosphate Phosphohydrolases><Guanosinetriphosphatases><Guanyl-Nucleotide Exchange Factor><Guanyl-Nucleotide Releasing Factor><Intracellular Communication and Signaling><Investigation><M Phase><Malignant Neoplasms><Malignant Tumor><Math Models><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Memory><Metabolic Diseases><Metabolic Disorder><Mitosis><Mitosis Stage><Mitotic><Model System><Nature><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Normal Cell><Oranges><Organism><Pattern><Phase><Property><Proteins><Recurrence><Recurrent><Regulation><Rod><S Period><S phase><S pombe><S. pombe><Schizosaccharomyces pombe><Second Gap Phase><Shapes><Signal Transduction><Signal Transduction Systems><Signaling><Site><Surface Proteins><Synthesis Period><Synthesis Phase><System><Testing><Therapeutic><Thesaurismosis><Tissue Growth><Tissues><biological signal transduction><cdc13 Protein><cell biology><cell growth><cellular polarity><developmental><exchange factor><guanosinetriphosphatase><insight><live cell image><live cell imaging><live cellular image><live cellular imaging><living system><malignancy><mathematic model><mathematical model><mathematical modeling><metabolism disorder><neoplasm/cancer><neuronal><new diagnostics><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation><next generation diagnostics><next generation therapeutics><novel diagnostics><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><ontogeny><p56cdc13><polarized cell><preservation><recruit><response><tool><yeast genetics>