Two Di-Leucine Motifs Regulate Trafficking of Mucolipin-1 to Lysosomes
| Autor: | Vergarajauregui, Silvia, Puertollano, Rosa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Amino Acid Motifs
Green Fluorescent Proteins Molecular Sequence Data Palmitic Acid TRPM Cation Channels di-leucine lysosomes Cytosol Transient Receptor Potential Channels Leucine Humans Amino Acid Sequence Cysteine Fluorescent Antibody Technique Indirect Alanine Microscopy Confocal MLIV Endocytosis Recombinant Proteins Protein Structure Tertiary Protein Transport Amino Acid Substitution Models Chemical mucolipin-1 Mutagenesis Site-Directed Traffic Interchange sorting HeLa Cells |
| Zdroj: | Traffic (Copenhagen, Denmark) |
| ISSN: | 1600-0854 1398-9219 |
| Popis: | Mutations in the mucolipin-1 gene have been linked to mucolipidosis type IV, a lysosomal storage disorder characterized by severe neurological and ophthalmologic abnormalities. Mucolipin-1 is a membrane protein containing six putative transmembrane domains with both its N- and C-termini localized facing the cytosol. To gain information on the sorting motifs that mediate the trafficking of this protein to lysosomes, we have generated chimeras in which the N- and C- terminal tail portions of mucolipin-1 were fused to a reporter gene. In this article, we report the identification of two separate di-leucine-type motifs that co-operate to regulate the transport of mucolipin-1 to lysosomes. One di-leucine motif is positioned at the N-terminal cytosolic tail and mediates direct transport to lysosomes, whereas the other di-leucine motif is found at the C-terminal tail and functions as an adaptor protein 2-dependent internalization motif. We have also found that the C-terminal tail of mucolipin-1 is palmitoylated and that this modification might regulate the efficiency of endocytosis. Finally, the mutagenesis of both di-leucine motifs abrogated lysosomal accumulation and resulted in cell-surface redistribution of mucolipin-1. Taken together, these results reveal novel information regarding the motifs that regulate mucolipin-1 trafficking and suggest a role for palmitoylation in protein sorting. |
| Databáze: | OpenAIRE |
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