Author ORCID Identifier

https://orcid.org/0000-0002-7198-6722

Date of Award

2023

Document Type

Thesis (Ph.D.)

Department or Program

Biochemistry and Cell Biology

First Advisor

Prachee Avasthi

Abstract

Cilia are structures present on most eukaryotic cells which provide important signaling and motile components to cells from early development to fully differentiated and matured cells. Regulation of these structures is critical to proper functioning of the cell and is known to be tied to the cell cycle. Preparation for ciliary assembly following cell cycle exit and ciliary disassembly following cell cycle reentry requires components throughout the cell body and within the cilium to facilitate this process. Here I identify how the cell adapts to ensure modifications to cilia occur for assembly or disassembly using the model organism Chlamydomonas reinhardtii. By chemically and genetically inhibiting map kinase phosphatases in Chlamydomonas which most closely match mammalian DUSP6, the phosphatase for ERK1/2 in the canonical cell cycle control ERK pathway, cilia shorten and fail to assemble. We find that DUSP6 inhibition also results in inhibited ciliary protein entry, altered protein localization to the transition zone, inhibited membrane trafficking or through inhibited cytoskeletal microtubule reorganization. Additionally, we find that maintaining cytoplasmic microtubules and short tracks of cilia can allow for cilia to immediately assemble within 5 minutes post deciliation. Together, this data provides a comprehensive view of how the cell induces changes outside of the cilium to regulate this critical signaling organelle.

Original Citation

Dougherty, L. L., Dutta, S., & Avasthi, P. (2023). The ERK activator, BCI, inhibits ciliogenesis and causes defects in motor behavior, ciliary gating, and cytoskeletal rearrangement. Life Science Alliance, 6(6), e202301899. https://doi.org/10.26508/lsa.202301899

Dougherty, L. L., & Avasthi, P. (2023). Determinants of cytoplasmic microtubule reorganization during ciliogenesis in Chlamydomonas reinhardtii [Preprint]. Cell Biology. https://doi.org/10.1101/2023.04.07.536038

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