An analysis of splicing, actin-binding properties, heterodimerisation and molecular interactions of the non-muscle {alpha}-actinins.

The non-muscle α-actinin isoforms (actinin-1 and -4) are closely related, dimeric actin filament-crosslinking 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 comprehensively compared these proteins in terms of alternative splicing, actin-binding properties, heterodimer formation and molecular interactions for the first time. We find that the calcium-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 calcium-insensitive variant of actinin-1. 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. Our findings 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.

Source: BJ Cell - April 4, 2013 Category: Biochemistry Authors: K Suzanne Foley, P W Young Tags: BJ Cell Source Type: research