The vacuolar-sorting protein Snf7 is required for export of virulence determinants in members of the Cryptococcus

Rodrigo M da C Godinho1, Juliana Crestani2, Lívia Kmetzsch3

  • 11] Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, Brazil [2].

Scientific Reports
|September 3, 2014
PubMed

Insights

The endosomal sorting complex required for transport (ESCRT) protein Snf7 is crucial for fungal virulence. Deleting Snf7 in Cryptococcus species impairs polysaccharide secretion and melanin production, leading to a loss of virulence.

Area of Science:

  • Mycology
  • Cell Biology
  • Pathogenesis

Background:

  • Fungal virulence relies on extracellular factors, with many lacking traditional secretory signals.
  • Unconventional secretion pathways are increasingly recognized as vital for fungal pathogenesis.
  • The endosomal sorting complex required for transport (ESCRT) machinery is implicated in exporting molecules in eukaryotic pathogens.

Purpose of the Study:

  • To investigate the role of the ESCRT component Snf7 in the virulence of Cryptococcus neoformans and Cryptococcus gattii.
  • To determine if Snf7 is involved in the unconventional secretion of virulence factors like polysaccharides and melanin.
  • To assess the impact of Snf7 deletion on fungal morphology and pathogenicity.

Main Methods:

  • Generation of snf7Δ mutant strains in Cryptococcus neoformans and Cryptococcus gattii.
  • Analysis of polysaccharide secretion, capsule formation, and melanin production in wild-type and mutant strains.
  • Evaluation of virulence in an intranasal murine infection model.

Main Results:

  • Deletion of Snf7 significantly altered polysaccharide secretion, capsule formation, and pigmentation in both fungal species.
  • snf7Δ mutants exhibited a complete loss of virulence in the murine infection model.
  • These findings indicate Snf7 is essential for the traffic of polysaccharides and melanin.

Conclusions:

  • Snf7 plays a critical role in regulating fungal virulence by controlling the unconventional secretion of polysaccharides and melanin.
  • Unconventional secretion mechanisms are essential for Cryptococcus pathogenesis.
  • The study highlights the importance of obscure export mechanisms for non-protein molecules in eukaryotes.

Related Concept Videos

Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.8K
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
2.4K
Overview of Protein Sorting and Transport01:45

Overview of Protein Sorting and Transport

Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation.  In gated transport, folded...
16.8K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.8K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.3K
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
3.9K