Hitchhiking vesicular transport routes to the vacuole: Amyloid recruitment to the Insoluble Protein Deposit (IPOD)

ABSTRACT

Sequestration of aggregates into specialized deposition sites occurs in many species across all kingdoms of life ranging from bacteria to mammals and is commonly believed to have a cytoprotective function. Yeast cells possess at least 3 different spatially separated deposition sites, one of which is termed “Insoluble Protein Deposit (IPOD)” and harbors amyloid aggregates. We have recently discovered that recruitment of amyloid aggregates to the IPOD uses an actin cable based recruitment machinery that also involves vesicular transport.¹ Here we discuss how different proteins known to be involved in vesicular transport processes to the vacuole might act to guide amyloid aggregates to the IPOD. These factors include the Myosin V motor protein Myo2 involved in transporting vacuolar vesicles along actin cables, the transmembrane protein Atg9 involved in the recruitment of large precursor hydrolase complexes to the vacuole, the phosphatidylinositol/ phosphatidylcholine (PI/PC) transfer protein Sec 14 and the SNARE chaperone Sec 18. Furthermore, we present new data suggesting that the yeast dynamin homolog Vps1 is also crucial for faithful delivery of the amyloid model protein PrD-GFP to the IPOD. This is in agreement with a previously identified role for Vps1 in recruitment of heat-denatured aggregates to a perivacuolar deposition site.²

KEYWORDS:

• actin
• amyloid aggregates
• Atg9 vesicles
• Cytoplasm-to-vacuole targeting (CVT) pathway
• Insoluble Protein Deposit (IPOD)
• Myosin motor protein Myo2
• prions
• Phagophore Assembly Site (PAS)
• Sec 14
• Sec 18
• vesicular transport
• Vps1
• yeast (Saccharomyces cerevisiae)

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DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

No potential conflicts of interest were disclosed.

ACKNOWLEDGMENTS

We thank the Imaging Facility of the Center for Molecular Biology Heidelberg (ZMBH) headed by Dr. Holger Lorenz for assistance with microscopic analyses. We also thank Prof. Bernd Bukau and members of his lab and Prof. Peter P. Nawroth and members of his lab for helpful discussions during the project.

FUNDING

This study was supported by the Deutsche Forschungsgemeinschaft to Jens Tyedmers (TY93/1–1).