The Unconventional Protein Secretion System, UPSS (Giuliani et al., 2011). IT secretes FGF1 (an annexin; TC#1.A.31) and Epimorphin (syntaxin 2; 8.A.91) (Hirai et al. 2007). GRASP55 regulates this unconventional secretion and aggregation of mutant huntingtin (Ahat et al. 2022). Golgi reassembly stacking proteins (GRASPs) regulate Golgi-independent unconventional secretion of certain cytosolic and transmembrane protein cargoes. Ahat et al. 2022 surveyed several neurodegenerative disease-related proteins, including mutant huntingtin (Htt-Q74), superoxide dismutase 1 (SOD1), tau, and TAR DNA-binding protein 43 (TDP-43), for unconventional secretion; Htt-Q74 was most robustly secreted in a GRASP55-dependent manner. Unconventional secretion of Htt is GRASP55 and autophagy dependent and is enhanced under stress conditions such as starvation and ER stress. GRASP55 facilitates Htt secretion by tethering autophagosomes to lysosomes to promote autophagosome maturation and subsequent lysosome secretion and by stabilizing p23/TMED10, a channel for translocation of cytoplasmic proteins into the lumen of the ER-Golgi intermediate compartment. Novel cytosolic cargoes secreted by the same unconventional pathway, include transgelin (TAGLN), multifunctional protein ADE2 (PAICS), and peroxiredoxin-1 (PRDX1) (Ahat et al. 2022). Golgi reassembly-stacking protein 2, (GRS2; GRASP55; Golgi phosphoprotein 6, GOLPH6) regulates this unconventional protein secretion (Ahat et al. 2022).
UPSS of Mus musculus
1) S100A13 Ca2+ binding protein (98 aas)(P97352)
2) p40Syt1 synaptogamin1 (homologous to 8.A.30.1.1) (421 aas)(P46096)
3) Small conductance Ca2+-activated K+ channel protein 1 (very similar to SK2 (1.A.1.16.1) (537 aas) (Q9EQR3)
4) Annexin II (A2) (339 aas) (P07356)
5) FGF1 Fibroblast Growth Factor; Heparin-binding growth factor (155 aas) (P61148)
6) Golgi reassembly - stacking protein 2, Gorasp2 or GRASP (451 aas) (Q99JX3)