Cytosolic PrP induces apoptosis of cell by disrupting microtubule assembly

Xiao-Li Li1, Gui-Rong Wang, Yuan-Yuan Jing

  • 1State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing, 100052, People's Republic of China.

Insights

Cytosolic prion protein (PrP) disrupts microtubule formation, leading to reduced cell viability and apoptosis. This cellular PrP accumulation impacts tubulin levels, suggesting a role in neuronal cell death.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Biochemistry

Background:

  • Prion protein (PrP) interacts with tubulin, affecting microtubule dynamics.
  • The precise role of cytosolic PrP in cellular processes remains unclear.

Purpose of the Study:

  • To investigate the impact of cytosolic prion protein accumulation on microtubule structure and cell viability.
  • To explore the relationship between PrP, tubulin, and apoptosis in cellular models and scrapie-infected brains.

Main Methods:

  • Transfection of HeLa cells with a plasmid expressing human PrP23-230.
  • Immunoprecipitation assays to detect PrP-tubulin interaction.
  • Confocal and immunofluorescent microscopy to visualize PrP and microtubule structures.
  • Assessment of cell viability and apoptosis.
  • Analysis of tubulin levels in scrapie-infected hamster brains.

Main Results:

  • Cytosolic PrP co-localizes with tubulin in the cytoplasm.
  • Accumulation of cytosolic PrP disrupts microtubule organization.
  • Reduced cell viability and increased apoptosis were observed in cells with cytosolic PrP.
  • Microtubule protein levels decreased in cells expressing cytosolic PrP.
  • Lower levels of endogenous tubulin were found in scrapie-infected hamster brains.

Conclusions:

  • Abnormal cytosolic PrP accumulation disrupts the microtubule framework, leading to cell death.
  • The microtubule-disrupting activity of cytosolic PrP is linked to apoptosis, potentially shedding light on PrP's neuronal function.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.