Transport of LAPTM5 to lysosomes requires association with the ubiquitin ligase Nedd4, but not LAPTM5 ubiquitination
| Autor: | M. Christine Bruce, Nam Pham, Daniela Rotin, Wioletta K. Glowacka, Youngshil Pak |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Nedd4 Ubiquitin Protein Ligases
Ubiquitin-Protein Ligases Amino Acid Motifs Golgi Apparatus NEDD4 macromolecular substances Plasma protein binding Biology Models Biological Article Mice 03 medical and health sciences symbols.namesake Ubiquitin Lysosome medicine Animals Humans Research Articles 030304 developmental biology 0303 health sciences Endosomal Sorting Complexes Required for Transport ADP-Ribosylation Factors 030302 biochemistry & molecular biology Membrane Proteins Dendritic Cells Cell Biology Golgi apparatus Cell biology Ubiquitin ligase Transport protein Adaptor Proteins Vesicular Transport Protein Transport medicine.anatomical_structure Biochemistry symbols biology.protein Mutant Proteins Lysosomes Protein Binding |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200603001 |
| Popis: | LAPTM5 is a lysosomal transmembrane protein expressed in immune cells. We show that LAPTM5 binds the ubiquitin-ligase Nedd4 and GGA3 to promote LAPTM5 sorting from the Golgi to the lysosome, an event that is independent of LAPTM5 ubiquitination. LAPTM5 contains three PY motifs (L/PPxY), which bind Nedd4-WW domains, and a ubiquitin-interacting motif (UIM) motif. The Nedd4–LAPTM5 complex recruits ubiquitinated GGA3, which binds the LAPTM5-UIM; this interaction does not require the GGA3-GAT domain. LAPTM5 mutated in its Nedd4-binding sites (PY motifs) or its UIM is retained in the Golgi, as is LAPTM5 expressed in cells in which Nedd4 or GGA3 is knocked-down with RNAi. However, ubiquitination-impaired LAPTM5 can still traffic to the lysosome, suggesting that Nedd4 binding to LAPTM5, not LAPTM5 ubiquitination, is required for targeting. Interestingly, Nedd4 is also able to ubiquitinate GGA3. These results demonstrate a novel mechanism by which the ubiquitin-ligase Nedd4, via interactions with GGA3 and cargo (LAPTM5), regulates cargo trafficking to the lysosome without requiring cargo ubiquitination. |
| Databáze: | OpenAIRE |
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