The spectrin–ankyrin–4.1–adducin membrane skeleton: adapting eukaryotic cells to the demands of animal life

Abstract

The cells in animals face unique demands beyond those encountered by their unicellular eukaryotic ancestors. For example, the forces engendered by the movement of animals places stresses on membranes of a different nature than those confronting free-living cells. The integration of cells into tissues, as well as the integration of tissue function into whole animal physiology, requires specialisation of membrane domains and the formation of signalling complexes. With the evolution of mammals, the specialisation of cell types has been taken to an extreme with the advent of the non-nucleated mammalian red blood cell. These and other adaptations to animal life seem to require four proteins--spectrin, ankyrin, 4.1 and adducin--which emerged during eumetazoan evolution. Spectrin, an actin cross-linking protein, was probably the earliest of these, with ankyrin, adducin and 4.1 only appearing as tissues evolved. The interaction of spectrin with ankyrin is probably a prerequisite for the formation of tissues; only with the advent of vertebrates did 4.1 acquires the ability to bind spectrin and actin. The latter activity seems to allow the spectrin complex to regulate the cell surface accumulation of a wide variety of proteins. Functionally, the spectrin-ankyrin-4.1-adducin complex is implicated in the formation of apical and basolateral domains, in aspects of membrane trafficking, in assembly of certain signalling and cell adhesion complexes and in providing stability to otherwise mechanically fragile cell membranes. Defects in this complex are manifest in a variety of hereditary diseases, including deafness, cardiac arrhythmia, spinocerebellar ataxia, as well as hereditary haemolytic anaemias. Some of these proteins also function as tumor suppressors. The spectrin-ankyrin-4.1-adducin complex represents a remarkable system that underpins animal life; it has been adapted to many different functions at different times during animal evolution.

Identification of cytoskeletal elements enclosing the ATP pools that fuel human red blood cell membrane cation pumps

“…Our results also raise the question of how the corrals that harbor the ATP pool relate to the known structures of the membrane-cytoskeletal complexes (22)(23)(24). The major RBC membrane complexes are of two types, a junctional complex and an ankyrin complex, with some overlap in the constituents of the two (25,26). The prime distinctions between the two complexes lie in the fact that the former contains actin, adducin, and protein 4.1, whereas the latter contains ankyrin.…”

Interaction between protein 4.1R and spectrin heterodimers

“…α-/β-spectrins, in the form of head-to-head tetramers, compose a lattice of cytoskeleton, which cross links other structural, linking and integral proteins within the membrane. Thus, spectrins play a central role in establishing the organization of the membrane skeleton (2,12). Mutations in spectrins lead to clinically significant forms of hereditary elliptocytosis and hereditary pyropoikilocytosis (13).…”

Mathematical-Computational Simulation of Cytoskeletal Dynamics

“…This research is in its infancy and a lot of open questions lay ahead, besides those related to model validation. These open questions include: (1) relations between the number of filaments in the bundle and several aspects, like flow velocity, G-actin concentration, elongation-retraction of the protrusion, etc; (2) the mechanical effects or the flow over the membrane throughout the filopodia; and (3) how the outward movement of the filament bundle affects the laminar inward flow. We are working towards joining the PIC and the finite volume algorithms and hope to be addressing these intriguing questions in the near future and couple them up with imaging experiments in Drosophila growth cones.…”

“…2.1). Capping proteins, such as CapZs or adducin, bind and stabilize the F-actin plus-end, i.e., suppress polymerization [1,16].…”