about the Cytoplasm-to-vacuole targeting (Cvt) pathway

Cytoplasm-to-vacuole targeting (Cvt) is a constitutive and specific form of autophagy that uses autophagosomal-like vesicles for selective transport of hydrolases aminopeptidase I (Lap4p) and alpha-mannosidase (Ams1p) to the vacuole (5, 6). Unlike autophagy, which is primarily a catabolic process, Cvt is a biosynthetic process. Like autophagosomes, Cvt vesicles form at a structure known as the phagophore assembly site (PAS) (also called the pre-autophagosomal structure). The PAS structure generates an isolation membrane (IM), which expands and eventually fuses along the edges to complete vesicle formation. At the vacuole, the outer membrane of the Cvt vesicle fuses with the vacuolar membrane, the vesicle is degraded, and the cargos are released and processed into their mature forms by vacuolar peptidases (reviewed in 7). The Cvt pathway has not been observed outside of yeast, and enzymes specifically involved in this pathway are not well conserved in other organisms (8 and references therein).

about ATG19

ATG19 encodes the receptor protein required for cargo loading in the cytoplasm-to-vacuole targeting (Cvt) pathway (3, 2). Atg19p binds to unprocessed, pro-forms of aminopeptidase I and alpha-mannosidase and brings them to the preautophagosomal structure (PAS), the origin of both autophagic and Cvt vesicles (4, 3, 9). PAS localization is dependent on Atg19p interactions with Atg11p, the Cvt adapter protein, and Atg8p, a ubiquitin-like protein which appears to be required for membrane tethering and hemifusion (10). Atg19p is incorporated, along with the cargo, into the Cvt vesicle and is eventually degraded by vacuolar proteinases (reviewed in 11).

Atg19p is ubiquitinated on two lysine residues, Lys(213) and Lys(216), and deubiquitinated in a Ubp3p-dependent manner. These post-translational modifications affect cargo affinity, and both ubiquitination and deubiquitination are required for full Atg19p activity (12). atg19 deletion mutants are defective in Cvt vesicle formation, and overexpression of ATG19 inhibits filamentous growth (13, 14). ATG19 homologs have only been identified in other Saccharomyces species and conservation is very low (<27%) (8).

about autophagy nomenclature

The initial identification of factors involved in autophagy was carried out by several independent labs, which led to a proliferation of nomenclature for the genes and gene products involved. The differing gene name acronyms from these groups included APG, AUT, CVT, GSA, PAG, PAZ, and PDD (1 and references therein). A concerted effort was made in 2003 by the scientists working in the field to unify the nomenclature for these genes, and "AuTophaGy-related" genes are now denoted by the letters ATG (1). In addition to the ATG gene names that have been assigned to S. cerevisiae proteins and their orthologs, several ATG gene names, including ATG25, ATG28, and ATG30, have been used to designate proteins in other ascomycete yeast species for which there is no identifiable equivalent in S. cerevisiae (8, 15).

Last updated: 2008-04-23