| First Author | Foley KS | Year | 2013 |
| Journal | Biochem J | Volume | 452 |
| Issue | 3 | Pages | 477-88 |
| PubMed ID | 23557398 | Mgi Jnum | J:198978 |
| Mgi Id | MGI:5499967 | Doi | 10.1042/BJ20121824 |
| Citation | Foley KS, et al. (2013) An analysis of splicing, actin-binding properties, heterodimerization and molecular interactions of the non-muscle alpha-actinins. Biochem J 452(3):477-88 |
| abstractText | The non-muscle alpha-actinin isoforms (actinin-1 and -4) are closely related dimeric actin filament cross-linking proteins. Despite high sequence similarity, unique properties have been ascribed to actinin-4 in particular. For example, actinin-4, but not actinin-1, is essential for normal glomerular function in the kidney, is overexpressed in several cancers and can translocate to the nucleus to regulate transcription. To understand the molecular basis for such isoform-specific functions we have, for the first time, comprehensively compared these proteins in terms of alternative splicing, actin-binding properties, heterodimer formation and molecular interactions. We find that the Ca2+-insensitive variant of actinin-4 is expressed only in the nervous system and thus cannot be regarded as a smooth muscle isoform, as is the case for the Ca2+-insensitive variant of actinin-1. The actin-binding properties of actinin-1 and -4 are similar and are unlikely to explain isoform-specific functions. Surprisingly, we reveal that actinin-1/-4 heterodimers, rather than homodimers, are the most abundant form of actinin in many cell lines. Finally, we use a proteomics approach to identify potential isoform-specific interactions. The results of the present study indicate that actinin-1 and -4 can readily form heterodimers composed of monomers that may have different properties and interacting proteins. This significantly alters our view of non-muscle actinin function. |
