PUBLICATION
Distinct amino acid motifs carrying multiple positive charges regulate membrane targeting of dysferlin and MG53
- Authors
- Zhou, L., Middel, V., Reischl, M., Strähle, U., Nienhaus, G.U.
- ID
- ZDB-PUB-180810-9
- Date
- 2018
- Source
- PLoS One 13: e0202052 (Journal)
- Registered Authors
- Middel, Volker, Strähle, Uwe
- Keywords
- none
- MeSH Terms
-
- Amino Acid Motifs*
- Amino Acids/chemistry*
- Animals
- Carrier Proteins/chemistry*
- Cell Membrane/metabolism
- Dysferlin/chemistry*
- HeLa Cells
- Humans
- Mice
- Microscopy, Confocal
- Muscle Proteins/metabolism
- Muscle, Skeletal/metabolism
- Mutation
- Protein Binding
- Protein Domains
- Sarcolemma/metabolism
- Tryptophan/chemistry
- Zebrafish
- PubMed
- 30092031 Full text @ PLoS One
Citation
Zhou, L., Middel, V., Reischl, M., Strähle, U., Nienhaus, G.U. (2018) Distinct amino acid motifs carrying multiple positive charges regulate membrane targeting of dysferlin and MG53. PLoS One. 13:e0202052.
Abstract
Dysferlin (Dysf) and mitsugumin53 (MG53) are two key proteins involved in membrane repair of muscle cells which are efficiently recruited to the sarcolemma upon lesioning. Plasma membrane localization and recruitment of a Dysf fragment to membrane lesions in zebrafish myofibers relies on the presence of a short, polybasic amino acid motif, WRRFK. Here we show that the positive charges carried by this motif are responsible for this function. In mouse MG53, we have identified a similar motif with multiple basic residues, WKKMFR. A single amino acid replacement, K279A, leads to severe aggregation of MG53 in inclusion bodies in HeLa cells. This result is due to the loss of positive charge, as shown by studying the effects of other neutral amino acids at position 279. Consequently, our data suggest that positively charged amino acid stretches play an essential role in the localization and function of Dysf and MG53.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping