Sarcomeric and nonmuscle α-actinin isoforms exhibit differential dynamics at skeletal muscle Z-lines
| Autor: | Alan H. Beggs, John H. Hartwig, Cynthia P. Hsu, Behzad Moghadaszadeh |
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| Rok vydání: | 2018 |
| Předmět: |
Sarcomeres
0301 basic medicine Gene isoform macromolecular substances Biology Article Mice 03 medical and health sciences Structural Biology medicine Animals Protein Isoforms Myocyte Actinin Muscle Skeletal Cytoskeleton Actin 030102 biochemistry & molecular biology EF hand Fluorescence recovery after photobleaching Skeletal muscle Cell Biology musculoskeletal system Fusion protein Cell biology Actin Cytoskeleton 030104 developmental biology medicine.anatomical_structure |
| Zdroj: | Cytoskeleton. 75:213-228 |
| ISSN: | 1949-3584 |
| Popis: | The α-actinin proteins are a highly conserved family of actin crosslinkers that mediate interactions between several cytoskeletal and sarcomeric proteins. Non-sarcomeric α-actinin-1 and α-actinin-4 crosslink actin filaments in the cytoskeleton, while sarcomeric α-actinin-2 and α-actinin-3 serve a crucial role in anchoring actin filaments to the muscle Z-line. To assess the difference in turnover dynamics and structure/function properties between the α-actinin isoforms at the sarcomeric Z-line, we used Fluorescence Recovery After Photobleaching (FRAP) in primary myofiber cultures. We found that the recovery kinetics of these proteins followed three distinct patterns: α-actinin-2/α-actinin-3 had the slowest turn over, α-actinin-1 recovered to an intermediate degree, and α-actinin-4 had the fastest recovery. Interestingly, the isoforms’ patterns of recovery were reversed at adhesion plaques in fibroblasts. This disparity suggests that the different α-actinin isoforms have unique association kinetics in myofibers and that non-muscle isoform interactions are more dynamic at the sarcomeric Z-line. Protein domain-specific investigations using α-actinin-2/4 chimeric proteins showed that differential dynamics between sarcomeric and non-muscle isoforms are regulated by cooperative interactions between the N-terminal actin-binding domain, the spectrin-like linker region and the C-terminal calmodulin-like EF hand domain. Together, these findings demonstrate that α-actinin isoforms are unique in binding dynamics at the Z-line and suggest differentially evolved interactive and Z-line association capabilities of each functional domain. |
| Databáze: | OpenAIRE |
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