26.3
Formação de Microtúbulos
Os microtúbulos são estruturas dinâmicas que passam por montagem e desmontagem contínuas. Eles se originam de complexos multiproteicos especializados…
A formação de microtúbulos começa em áreas especializadas dentro das células, os centros organizadores de microtúbulos ou MTOCs.
As células eucarióticas têm vários tipos de MTOCs, incluindo corpos basais e centrossomas, que recrutam proteínas que compõem os complexos do anel gama-tubulina.
Primeiro, duas subunidades de gama-tubulina se acoplam a duas diferentes proteínas do complexo gama-tubulina ou GCPs formando um núcleo heterotetramérica - o pequeno complexo gama-tubulina. Em seguida, sete cópias desse complexo central se organizam em uma estrutura helicoidal e se associam a outros GCPs acessórios para formar o complexo completo do anel gama-tubulina.
O complexo de anéis resultante tem treze subunidades expostas de gama-tubulina que atuam como um modelo para a formação de microtúbulos.
A nucleação dos microtúbulos começa quando a alfa-tubulina se liga às subunidades expostas da gama-tubulina formando a extremidade negativa do complexo do anel. Isso deixa a beta-tubulina, ou a extremidade positiva do heterodímero, livre para montagem posterior.
O complexo do anel gama-tubulina no filamento da extremidade negativa atua como uma tampa e permite que o alongamento prossiga apenas na extremidade positiva.
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Q1: What are microtubule organizing centers and what role do they play in microtubule formation?
Microtubule organizing centers (MTOCs) are specialized cellular structures where microtubule formation begins. In eukaryotic cells, MTOCs include centrosomes and basal bodies that recruit gamma-tubulin ring complexes. These complexes serve as templates for microtubule nucleation, with the minus end anchored at the MTOC and the plus end extending outward for continued assembly.
Q2: How is the gamma-tubulin ring complex assembled?
The gamma-tubulin ring complex forms through a multi-step process. First, two gamma-tubulin subunits couple with two Gamma-tubulin-Complex-Proteins (GCPs) to create a heterotetrameric core. Seven copies of this core arrange helically and associate with additional accessory GCPs, resulting in a complete ring complex with thirteen exposed gamma-tubulin subunits that template microtubule formation.
Q3: What happens when alpha-tubulin binds to the gamma-tubulin ring complex?
When alpha-tubulin binds to exposed gamma-tubulin subunits, it initiates microtubule nucleation and forms the minus end of the microtubule. This binding leaves the beta-tubulin (plus end) of the heterodimer free for further assembly. The gamma-tubulin ring complex acts as a cap at the minus end, restricting elongation to occur only at the plus end.
Q4: What is the difference between the minus end and plus end of a microtubule?
The minus end originates at the MTOC where alpha-tubulin binds to the gamma-tubulin ring complex, serving as the nucleation site. The plus end extends outward from the MTOC and is the primary site for microtubule elongation. This polarity allows directional microtubule growth and is essential for organizing spindle complexes during cell division.
Q5: How do intrinsic and extrinsic factors influence microtubule nucleation?
Intrinsic factors affecting nucleation include alpha- and beta-tubulin isotypes, free heterodimer concentration, post-translational modifications, and microtubule-associated proteins (MAPs). Extrinsic factors such as temperature, pH, and microtubule interfering drugs regulate polymerization and depolymerization rates. Together, these factors control the dynamics of microtubule assembly within the cell.
Q6: What are the primary functions of microtubules in eukaryotic cells?
Microtubules serve two main functions: organizing spindle complexes to separate sister chromatids during mitotic or meiotic cell division, and forming locomotory appendages like cilia and flagella. Their dynamic nature allows continuous assembly and disassembly, enabling cells to rapidly reorganize these structures in response to cellular needs.
Q7: How do MTOCs vary across different eukaryotic cell types?
The structure and location of MTOCs vary within different eukaryotic cell types depending on microtubule function. Animal cells contain organized centrosomes with centrioles and pericentriolar material, while some lower eukaryotes like most fungi lack organized MTOCs entirely. This variation reflects the specialized roles microtubules play in different cell types.