Cell vaults: the next big thing in biology?

Cell vaults: the next big thing in biology?

The activity of a cell is organised by a range of structures, from large organelles to small protein complexes. Amongst these, each cell contains around 100,000 cellular vaults, or simply vaults. These are enigmatic mid-size symmetrical cellular ribonucleoprotein structures that play a role in the storage and transport of molecules within cells.

Discovery

The discovery of cell vaults dates back to the late 20th century when researchers were investigating the intracellular transport mechanisms. Initially, these structures were not well understood, and their function was largely speculative. Advances in microscopy and molecular biology techniques have allowed scientists to study these structures in greater detail. However, their precise function remains enigmatic.

The term “vault” was coined due to the double vault-like shape of these structures, which resemble the architectural vaults found in buildings. The discovery of vaults was significant because it added a new dimension to our understanding of intracellular transport and storage mechanisms. Their name is perhaps also appropriate as these structures provide cellular stores.

Composition of Cell Vaults

Cell vaults are large ribonucleoprotein particles (combinations of RNA and RNA binding protein), approximately 40 x 70 nm, several times larger than ribonucleoprotein complexes (RNPs). Like RNPs, vaults are composed of both RNA and protein components. The primary protein component of vaults is known as the major vault protein (MVP) which contains more than 800 amino acids. 78 copies of MVP forms the structural backbone of the vault. In the above image, one of these is coloured white. The vault structure is typically composed of multiple MVP subunits, which assemble into a hollow, barrel-like shape. This unique architecture allows vaults to encapsulate various molecules, protecting them from the cellular environment. The vault’s size and shape can vary, but they are generally large enough to accommodate a variety of molecular cargo.

In addition to MVP, vaults contain two other proteins: vault poly(ADP-ribose) polymerase (VPARP) and telomerase-associated protein 1 (TEP1). These proteins are thought to play roles in the regulation of vault function and the interaction with other cellular components. The RNA component of vaults, known as vault RNA (vRNA), is relatively small and its exact function is still under investigation, though it may be involved in the regulation of vault assembly and function.

How many?

Each cell contains about 100,000 vaults although immune cells, for example, can contain many more. An increase in vault protein numbers is associated with diseases such as drug-resitant cancer. 

Function of Cell Vaults

The primary function of cell vaults is not clear, but evidence supports a role in the transport and storage of molecules within the cell. Vaults are thought to protect their cargo from degradation and facilitate the transport of molecules to specific cellular locations. This may be particularly important for the regulation of cellular processes that require precise timing and localization of molecular interactions.

Vaults are implicated in several cellular processes, including:

  • Intracellular Transport: Vaults are thought to act as transport vehicles within the cell, shuttling molecules such as proteins and RNA to specific locations. This is crucial for maintaining cellular organization and ensuring that biochemical processes occur in the right place at the right time.
  • Detoxification and Drug Resistance: Vaults have been associated with the cellular response to toxins and drugs. They may sequester harmful substances, thereby protecting the cell from damage. This function is particularly relevant in the context of cancer, where vaults have been implicated in the development of drug resistance.
  • Immune Response: Some studies suggest that vaults may play a role in the immune response, possibly by transporting signalling molecules that modulate immune activity. This function is still under investigation, but it highlights the potential versatility of vaults in cellular processes.
  • Cellular Stress Response: Vaults may help cells cope with stress by sequestering and protecting critical molecules during adverse conditions. This protective role is essential for cell survival under stress, such as oxidative stress or nutrient deprivation.

Significance and Applications of Cell Vaults

The study of cell vaults has significant implications for both basic biology and medical applications. Understanding the function and regulation of vaults can provide insights into fundamental cellular processes and how cells maintain homeostasis. Additionally, the unique properties of vaults make them attractive candidates for various biotechnological and therapeutic applications.

  • Drug Delivery Systems: Due to their ability to encapsulate and transport molecules, vaults are being explored as potential drug delivery vehicles. Their natural ability to protect and transport cargo within cells can be harnessed to deliver therapeutic agents directly to target cells, potentially allowing improved delivery of RNA drugs which could be loaded into empty vaults.
  • Cancer Research: Given their role in drug resistance, vaults are of particular interest in cancer research. Understanding how vaults contribute to the resistance mechanisms can lead to the development of strategies to overcome resistance and improve the effectiveness of chemotherapy.
  • Biomarker Discovery: Vaults and their components may serve as biomarkers for certain diseases. Changes in the expression or function of vaults could indicate the presence of disease or the response to treatment, providing valuable diagnostic and prognostic information.
  • Synthetic Biology: The structural properties of vaults make them intriguing candidates for synthetic biology applications. Researchers are exploring ways to engineer vaults to carry specific molecules or to perform novel functions within cells. This could lead to the development of new tools for research and therapeutic interventions.
  • Nanotechnology: The robust and versatile structure of vaults makes them suitable for applications in nanotechnology. They can be engineered to serve as nanoscale containers or scaffolds, potentially useful in a variety of fields, from materials science to medicine.

 IMAGE The symmetrical structure of a vault. The external structure is composed of 78 copies of the major vault protein, one of which is highlighted.  CREDIT Protein Database

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