Unveiling the Process of Stable Microtubule Bundle Formation in Quiescent Yeast

Core Concepts

The author explores the multistep process of stable microtubule bundle formation in quiescent yeast, highlighting the sequential actions of specific kinesins and kinetochore interactions. The main thesis is to provide a detailed molecular-scale description of the life cycle of a stable microtubule structure in vivo.

Abstract

The content delves into the intricate process of forming stable microtubule bundles in quiescent yeast cells. It reveals the involvement of specific kinesins, kinetochore interactions, and temporal sequences leading to bundle assembly and disassembly. The study sheds light on the physiological functions and regulatory mechanisms underlying this unique cellular structure. Cells fine-tune microtubule assembly to create distinct structures with specific functions. In proliferating cells, dynamic microtubules are crucial for various cellular processes. Stable microtubules networks are essential for cell shape maintenance and intracellular transport. Defects in microtubule stabilization can lead to human pathologies like neurodegenerative diseases. Yeast species have been instrumental in unraveling mechanisms regulating microtubule dynamics. Quiescent yeast cells assemble stable parallel microtubules known as Q-nMT bundles. Formation of Q-nMT bundles involves a multistep process driven by specific kinesins and kinetochore interactions. Kinetochore components play a critical role in initiating Q-nMT bundle formation upon entry into quiescence. Each phase of Q-nMT bundle formation requires specific kinesins for nucleation, elongation, and stabilization. Disassembly of Q-nMT bundles precedes SPB duplication/separation upon exit from quiescence.

Stats

MTs elongated from SPB reach ≈ 0.8 µm during phase I-MTs assembly. Additional MTs emerge from SPB during phase II-MTs elongation along phase I-MTs. Complete stabilization achieved ≈ 48h after glucose exhaustion (phase III). Tub4 accumulates at SPB during phase I initiation.

Quotes

"Cells fine-tune these mechanisms in both space and time to give rise to distinct MT edifices with specific functions." "In proliferating cells, dynamic MTs allow exploration of cell volume for various cellular processes." "Defects in MT stabilization are linked to human pathologies like neurodegenerative diseases."

Key Insights Distilled From

A stable microtubule bundle formed through an orchestrated multistep process controls quiescence exit

by Laporte,D., ... at www.biorxiv.org 05-03-2023

https://www.biorxiv.org/content/10.1101/2023.05.02.539064v4

Deeper Inquiries

What implications could understanding stable microtubule structures have for developing treatments for neurodegenerative diseases

Understanding stable microtubule structures could have significant implications for developing treatments for neurodegenerative diseases. In many neurodegenerative conditions, such as Alzheimer's disease and Parkinson's disease, there is evidence of cytoskeletal defects and disrupted microtubule dynamics in affected neurons. By studying the molecular mechanisms involved in stabilizing microtubule structures, researchers may uncover new targets for therapeutic interventions aimed at restoring normal cytoskeletal function in these diseases. For example, identifying key proteins or pathways that regulate stable microtubule formation could lead to the development of drugs that enhance microtubule stability or prevent pathological changes associated with neurodegeneration.

How might disruptions in kinetochore interactions impact other cellular processes beyond microtubule dynamics

Disruptions in kinetochore interactions can have far-reaching effects beyond just impacting microtubule dynamics within cells. Kinetochore-microtubule attachments are crucial for proper chromosome segregation during cell division, ensuring accurate distribution of genetic material to daughter cells. Any disturbances in kinetochore function can lead to chromosomal instability, aneuploidy, and ultimately contribute to the development of cancer or other genetic disorders. Additionally, since kinetochores play a role in signaling pathways that monitor cell cycle progression and respond to errors during mitosis, disruptions in kinetochore interactions can also impact cell cycle regulation and cellular homeostasis.

How could studying yeast models help uncover novel therapeutic targets for human pathologies related to cytoskeletal defects

Studying yeast models provides a valuable platform for uncovering novel therapeutic targets for human pathologies related to cytoskeletal defects due to several reasons: Conservation of Cellular Processes: Many fundamental cellular processes are conserved between yeast and higher eukaryotes like humans. Therefore, insights gained from studying yeast models can often be translated into understanding similar processes in human cells. Genetic Manipulation: Yeast cells offer a powerful system for genetic manipulation which allows researchers to easily introduce mutations or deletions into specific genes of interest. This enables the study of gene functions and their roles in various cellular processes related to cytoskeletal dynamics. High-throughput Screening: Yeast models allow for high-throughput screening approaches where large numbers of genetic variants or compounds can be tested rapidly and efficiently. This facilitates the identification of potential therapeutic targets or drug candidates for treating human pathologies associated with cytoskeletal defects. Functional Conservation: Despite differences between yeast and human biology, many essential cellular functions are conserved across species including those related to the cytoskeleton. Studying how certain genes or proteins affect cytoskeletal organization in yeast can provide valuable insights into similar mechanisms at work in human cells. By leveraging these advantages offered by yeast models, researchers can identify novel therapeutic targets relevant to human diseases linked with abnormalities in the cytoskeleton like neurodegenerative disorders or cancer metastasis involving altered microtubules dynamics among others