mCLCA4 ER processing and secretion requires luminal sorting motifs
| Autor: | Mark S. Roberson, Haitao Sun, Bo Shui, Randolph C. Elble, Michael I. Kotlikoff, Gwendolyn Spizz, Kai Su Greene, Patricia J. Fisher, Robert Doran, Chunlei Huan |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Physiology
Recombinant Fusion Proteins Amino Acid Motifs Green Fluorescent Proteins Molecular Sequence Data CHO Cells Protein Sorting Signals Biology Endoplasmic Reticulum Cell Line Cell membrane Cricetulus Chloride Channels Cricetinae medicine Animals Humans Secretion Amino Acid Sequence Phosphorylation Peptide sequence Endoplasmic reticulum Cell Membrane Cell Biology biology.organism_classification Transport protein Protein Transport medicine.anatomical_structure Biochemistry Mutation Chloride channel Protein and Vesicle Trafficking Cytoskeleton |
| Zdroj: | American Journal of Physiology-Cell Physiology. 295:C279-C287 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00060.2008 |
| Popis: | Ca+-activated Cl− channel (CLCA) proteins are encoded by a family of highly related and clustered genes in mammals that are markedly upregulated in inflammation and have been shown to affect chloride transport. Here we describe the cellular processing and regulatory sequences underlying murine (m) CLCA4 proteins. The 125-kDa mCLCA4 gene product is cleaved to 90- and 40-kDa fragments, and the NH2- and COOH-terminal fragments are secreted, where they are found in cell media and associated with the plasma membrane. The 125-kDa full-length protein is only found in the endoplasmic reticulum (ER), and specific luminal diarginine retention and dileucine forward trafficking signals contained within the CLCA4 sequence regulate export from the ER and proteolytic processing. Mutation of the dileucine luminal sequences resulted in ER trapping of the immaturely glycosylated 125-kDa peptide, indicating that proteolytic cleavage occurs following recognition of the trafficking motifs. Moreover, the mutated dileucine and diarginine signal sequences directed processing of a secreted form of enhanced green fluorescent protein in a manner consistent with the effects on mCLCA4. |
| Databáze: | OpenAIRE |
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