Abstract
Actin bundling protein 34 (ABP34) is the one of 11 actin-crosslinking proteins identified in Dictyostelium discoideum, a novel model organism for the study of actin-associated neurodegenerative disorders such as Alzheimer's disease and Huntington's disease. ABP34 localizes at the leading and trailing edges of locomotory cells, i.e., at the cell cortex, filopodia, and pseudopodia. Functionally, it serves to stabilize membrane-associated actin at sites of cell–cell contact. In addition, this small crosslinking protein is involved in actin bundle formation, and its bundling activity is regulated by the concentration of calcium ion. Several studies have sought to determine the mechanism underlying the calcium-regulated actin bundling activity of ABP34, but it remains unclear. Using several mutational and structural analyses, we revealed that calcium binding to the EF2 motif disrupts the inter-domain interaction between the N- and C-domains, thereby inhibiting the actin bundling activity of ABP34. This finding provides clues about the pathogenesis of neurodegenerative disorders related to actin bundling.
| Original language | English |
|---|---|
| Pages (from-to) | 1836-1840 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 503 |
| Issue number | 3 |
| DOIs | |
| State | Published - 10 Sep 2018 |
Bibliographical note
Funding Information:Authors thank Dr. S Lee for providing plasmid with assisting data analysis. This study was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science , ICT & Future Planning ( NRF-2015R1C1A1A01053611 and 2018R1D1A1B07045580 to H. S Jung, and NRF-2017M3A9G7072417 to D. Jeoung).
Publisher Copyright:
© 2018 Elsevier Inc.
Keywords
- Actin bundling protein
- Actin-binding protein
- Actin-crosslinking protein
- EF-Hand
- Protein structure