attachment of mitotic spindle microtubules to kinetochore

Definition

Target type: biologicalprocess

The cellular process in which spindle microtubules become physically associated with the proteins making up the kinetochore complex in mitosis. [GOC:ai, GOC:clt, GOC:dph, GOC:tb, PMID:26258632, PMID:26705896]

The attachment of mitotic spindle microtubules to kinetochores is a crucial step in cell division, ensuring that chromosomes are accurately segregated to daughter cells. This process involves a complex interplay of molecular components and dynamic interactions.

**1. Kinetochore Formation:**
- During prophase, the centromere region of each chromosome becomes condensed and forms a specialized protein structure called the kinetochore.
- Kinetochores are composed of multiple layers:
- **Inner kinetochore:** Directly attached to the centromeric DNA, containing proteins that recognize and bind to centromeric DNA.
- **Outer kinetochore:** Interacts with microtubules and contains proteins that mediate microtubule binding.

**2. Microtubule Capture:**
- Microtubules emanating from the spindle poles, called kinetochore microtubules (K-fibers), begin to search for kinetochores.
- The capture of K-fibers by kinetochores is facilitated by:
- **Kinesin-related proteins:** Motor proteins that move along microtubules and bring kinetochores closer to the spindle poles.
- **Ndc80 complex:** A protein complex that directly binds to microtubules and promotes their stable attachment to kinetochores.

**3. Microtubule Attachment and Stability:**
- Once captured, K-fibers attach to the kinetochore in a highly regulated manner.
- **Lateral attachment:** Microtubules attach to the sides of the kinetochore, allowing for initial capture.
- **End-on attachment:** Microtubules attach to the end of the kinetochore, forming a stable, "monopolar" attachment.
- **Microtubule dynamics:** Microtubules undergo continuous cycles of polymerization and depolymerization, which contribute to the dynamic instability of kinetochore attachments.

**4. Sister Chromatid Bi-Orientation:**
- For proper chromosome segregation, each kinetochore must be attached to a microtubule from opposite poles of the spindle, a process called bi-orientation.
- **Tension sensing:** Kinetochores can sense tension generated by the opposing forces of microtubules pulling on sister chromatids.
- **Error correction mechanisms:** When attachment errors occur (e.g., single-pole attachment), cells have mechanisms to correct them, ensuring bi-orientation.

**5. Microtubule Depolymerization and Chromosome Movement:**
- During anaphase, the microtubules attached to kinetochores begin to depolymerize, pulling sister chromatids toward opposite poles of the cell.
- **Kinesin-13:** A motor protein that promotes microtubule depolymerization, contributing to chromosome movement.
- **Aurora B kinase:** A kinase that regulates microtubule dynamics and ensures proper chromosome alignment.

The precise molecular details of kinetochore-microtubule attachment are still being elucidated. However, this complex process is essential for ensuring accurate chromosome segregation during cell division, maintaining genetic stability, and preventing developmental abnormalities.'
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