Presenter: A/Prof Grant W. Booker

University: The University of Adelaide

Time: 16:30-17:30, 26 May, 2011

Venue: A203, Institute of Microbiology, Chinese Academy of Sciences

Abstract:

α-actinin-4 is a member of the spectrin superfamily and binds filamentous actin (F-actin). In humans, four isoforms ofα-actinin have been identified and divided into muscle (calcium-insensitive) and non-muscle isoforms (calcium-sensitive). α-actinin-2 and 3 are expressed specifically in cardiac and skeletal muscle cells, forming part of the contractile machinery. The non-muscle isoforms, α-actinin-1 and 4, are expressed ubiquitously, and are involved in actin filament bundling and binding to integins in focal adhesions. Mouse knockout studies have shown thatα-actinin-4 is required for podocyte formation in the kidney.

The structure ofα-actinin-4 comprises three functional regions: two adjacent calponin homology (CH) domains at the N-terminus for F-actin binding, four spectrin-like repeats in the central region for dimersiation and a calmodulin-like domain at the C-terminus for Ca2+ binding. It is organised as an anti-parallel homodimer formed by the interaction of four spectrin-like repeats between the two molecules to provide actin-binding regions at both ends. Our studies have shown how the membrane lipid phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] is able to regulate the interaction betweenα-actinin-4 and F-actin.