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Reconstitution of a Kv Channel into Lipid Membranes for Structural and Functional Studies
Published on: July 13, 2013
Short elements with charged amino acids form clusters to sort protachykinin into large dense-core vesicles
Guo-Qiang Ma1, Bin Wang, Hai-Bo Wang
1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Traffic (Copenhagen, Denmark)
|October 23, 2008
Summary
Clustered charged amino acids in protachykinin act as aggregative signals, efficiently sorting neuropeptides into large dense-core vesicles (LDCVs) for regulated secretion.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neuropeptide tachykinins are sorted into large dense-core vesicles (LDCVs) for regulated secretion from neurons.
- The precise mechanism governing protachykinin sorting into LDCVs remains unclear.
Purpose of the Study:
- To elucidate the mechanism of protachykinin sorting into LDCVs.
- To identify specific sequences or elements responsible for LDCV localization.
Main Methods:
- Truncation experiments were performed on protachykinin to identify functional domains.
- Analysis of amino acid distribution, particularly charged residues, within protachykinin.
- Investigation of the effects of neutral amino acid substitution on LDCV localization.
- Determination of optimal conditions for protachykinin aggregation.
Main Results:
- Both the propeptide and mature peptide regions of protachykinin are sorted into LDCVs.
- Charged amino acid clusters within these regions are crucial for LDCV sorting.
- A short element of 4-5 amino acids with two charged residues functions as a basic unit for LDCV sorting.
- Intermolecular aggregation, enhanced by clustered charged elements, is critical for efficient sorting.
- Optimal aggregation occurs at millimolar Ca(2+) and pH 5.5-6.0.
Conclusions:
- Clustered charged short elements in protachykinin act as aggregative signals for LDCV sorting.
- This mechanism regulates the efficiency of protachykinin sorting into the regulated secretory pathway.
- Identified a novel sorting mechanism for neuropeptides into LDCVs.
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