| Autor: |
Kishor, Chandan, Spillings, Belinda L., Luhur, Johana, Lutomski, Corinne A., Lin, Chi-Hung, McKinstry, William J., Day, Christopher J., Jennings, Michael P., Jarrold, Martin F., Mak, Johnson |
| Zdroj: |
JACS Au; February 2022, Vol. 2 Issue: 2 p522-530, 9p |
| Abstrakt: |
Polarized or precision targeting of protein complexes to their destinations is fundamental to cellular homeostasis, but the mechanism underpinning directional protein delivery is poorly understood. Here, we use the uropod targeting HIV synapse as a model system to show that the viral assembly machinery Gag is copolarized with the intracellular calcium (Ca2+) gradient and binds specifically with Ca2+. Conserved glutamic/aspartic acids flanking endosomal sorting complexes required for transport binding motifs are major Ca2+binding sites. Deletion or mutation of these Ca2+binding residues resulted in altered protein trafficking phenotypes, including (i) changes in the Ca2+–Gag distribution relationship during uropod targeting and/or (ii) defects in homo/hetero-oligomerization with Gag. Mutation of Ca2+binding amino acids is associated with enhanced ubiquitination and a decline in virion release via uropod protein complex delivery. Our data that show Ca2+–protein binding, via the intracellular Ca2+gradient, represents a mechanism that regulates intracellular protein trafficking. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
