High impact information on TLG2

• The SM protein Vps45p binds its Sx Tlg2p in a manner analogous to that captured by the Sly1p-Sed5p crystal structure, whereby the NH2-terminal peptide of the Sx inserts into a hydrophobic pocket on the outer face of domain I of the SM protein [1].
• Studies of the yeast trans-Golgi network (TGN)/endosomal SNARE complex, which includes the syntaxin-like SNARE Tlg2p, have suggested that its assembly requires activation by binding of the SM protein Vps45p to the cytoplasmic region of Tlg2p folded into a closed conformation [2].
• The t-SNARE in a late Golgi compartment (Tlg2p) syntaxin is required for endocytosis and localization of cycling proteins to the late Golgi compartment in yeast [3].
• Fractionation and protease protection experiments indicate that Tlg2p is required prior to or at the step of API segregation into the Cvt vesicle [4].
• We describe here the remaining two, Tlg1p and Tlg2p [5].

Biological context of TLG2

• TLG2 is not an essential gene, and its deletion does not cause defects in the secretory pathway [6].
• Since a deltavps45 deltatlg2 double mutant has a more severe vacuolar protein sorting defect than a deltatlg2 mutant, Vps45p cannot only interact with Tlg2p [7].
• These results strongly suggest that Tlg2p is a t-SNARE involved in early endosome biogenesis [6].
• Finally, we found that mutation of single PKA sites in Tlg1 (Ser31 to Ala31) or Tlg2 (Ser90 to Ala90) was sufficient to restore endocytosis, but not exocytosis, to snc cells [8].

Anatomical context of TLG2

• In addition, we report that Tlg2p forms a SEC18-dependent SNARE complex with Snc2p, a vesicle SNARE known to function in Golgi to plasma membrane trafficking [9].
• Besides Sed5p two others, Tlg1p and Tlg2p, are found in the Golgi complex [10].

Other interactions of TLG2

• Notably, Snc1(ala43) was found to be nonfunctional in cells lacking Tlg1 or Tlg2 [11].
• The Sec1p homologue Vps45p binds to the syntaxin Tlg2p [7].
• Thus, the early Vps45-Tlg2p-dependent step of the Cvt pathway appears to be mechanistically distinct from the comparable stage in macroautophagy [4].
• However, its deletion in cells lacking the vacuolar ATPase subunit Vma2p leads to loss of viability, suggesting that Tlg2p is involved in endocytosis [6].
• However, Snc2p binds in vivo to many other syntaxin-like t-SNAREs, and binding of Sncp to the endosomal/Golgi t-SNARE Tlg2p is also reduced in sec4-8 cells [12].

References