Alpha-Adducin - Assembling the cytoskeleton meshwork that underlies the plasma membrane

Mon, 09/21/2015 - 14:12

The structure and organization of the plasma membrane is maintained by an underlying network of cytoskeletal proteins including actin and spectrin. Adducin, a member of this protein network, binds to bundles and caps actin filaments and links them to spectrin. Adducin’s role in organizing the cytoskeletal meshwork at the plasma membrane is important in signal transduction, cell-cell adhesion, and cell migration (1). Adducins exist in three different isoforms: alpha, beta and gamma. These isoforms assemble into heterodimers that vary depending on cell type. Adducin was first characterized in red blood cells where it is made up of alpha and beta subunits. In most other cells adducin heterodimers are assembled from alpha and gamma subunits (2). Each subunit contains an N-terminal head domain, a middle neck region, and a C-terminal protease-sensitive tail domain. The C-terminus contains a conserved myristoylated alanine-rich C kinase substrate (MARCKS)-related domain (3). Phosphorylation of this domain by protein kinase C regulates adducin binding to actin/spectrin. These regulatory events have been investigated through studies with phospho-specific alpha-adducin antibodies (3). Adducin regulation can also be mediated through interactions with calmodulin. Examination of protein localization using alpha-adducin antibodies has shown general association with the cytoskeleton along with presence at the plasma membrane and adherens junctions (4). Additionally, these alpha-adducin antibodies also stain the nucleus in some cell lines examined, indicating nuclear localization at least under certain circumstances (4). In addition to this function in basic cell structure, adducin has been shown to be involved in hypertension. Adducin mutations are associated with misregulation of sodium and potassium ions in the kidney which leads to hypertension (1). This adducin function offers a potential therapeutic strategy for treatment of certain forms of hypertension. A recent study from Harvard medical school found alpha-adducin in complex with a Na/K ATPase in neuronal cells (5). Their experiments used an alpha-adducin antibody to show this complex was enriched under conditions known to cause neurodegenerative disorders. These results reveal a new role for alpha-adducin in neurobiology and hint at a potential mechanism for alpha-adducin’s function in hypertension and regulation of Na/K levels. While alpha-adducin plays a role in various disease states, its function in basic cell biology is also an important area of study. A recent article in the Journal of Cell Biology identified a novel role of alpha-adducin in mitotic spindle assembly and cell division (6). This study used general and phospho-specific alpha-adducin antibodies for immunofluorescence and immunoprecipitations to monitor localization and phosphorylation during cell division. Their results demonstrated an interaction with myosin-X that is regulated by alpha-adducin phosphorylation and is important for spindle assembly.

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  1. 16207143
  2. 11895774
  3. 10950304
  4. 25978380
  5. 25344630
  6. 24379415

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