Signal transmission through elements of the cytoskeleton form an optimized information network in eukaryotic cells

Abstract

Multiple prior empirical and theoretical studies have demonstrated wire-like flow of electrons and ions along elements of the cytoskeleton but this has never been linked to a biological function. Here we propose that eukaryotes use this mode of signal transmission to convey spatial and temporal environmental information from the cell membrane to the nucleus. The cell membrane, as the interface between intra- and extra-cellular environments, is the site at which much external information is received. Prior studies have demonstrated that transmembrane ion gradients permit information acquisition when an environmental signal interacts with specialized protein gates in membrane ion channels and producing specific ions to flow into or out of the cell along concentration gradients. The resulting localized change in cytoplasmic ion concentrations and charge density can alter location and enzymatic function of peripheral membrane proteins. This allows the cell to process the information and rapidly deploy a local response. Here we investigate transmission of information received and processed in and around the cell membrane by elements of the cytoskeleton to the nucleus to alter gene expression. We demonstrate signal transmission by ion flow along the cytoskeleton is highly optimized. In particular, microtubules, with diameters of about 30 nm, carry coarse-grained Shannon information to the centrosome adjacent to the nucleus with minimum loss of input source information. And, microfilaments, with diameters of about 4 nm, transmit maximum Fisher (fine-grained) information to protein complexes in the nuclear membrane. These previously unrecognized information dynamics allow continuous integration of spatial and temporal environmental signals with inherited information in the genome.

Figure 1

Information dynamics in and around the cell membrane and transmission to central organelles. The resting state of the membrane, with large transmembrane concentration gradients of K+, Na+ and Cl− is shown in the upper left panel. In the lower left panel, an environmental signal causes the gates in transmembrane K+ channels to open. This allows rapid flow of K+ out of the cell briefly altering the ion concentrations and charge balance in the cytoplasm. Prior studies have shown these ion dynamics alter localization and function of peripheral membrane proteins permitting analysis of and response to the environmental perturbation. This ion flux in the cytoplasm adjacent to the cell membrane can also enter the channel of adjacent microtubules which allows transmission of coarse-grained information to the centrosome (see Fig. 3). The ion flux can also change the electrical potential at the distal end of a microfilament allowing electron flow along the wire-like structure transmitting (Fig. 3) fine-grained information to a protein complex in the nuclear membrane which can alter gene expression and chromosomal location.

Figure 2

Distribution of microfilaments and microtubules in eukaryotes. Immunohistochemistry stains showing the distribution of microtubules (green) and microfilaments (red) within normal fibroblasts.

Figure 3

Cytoskeletal structures as information conduits. An environmental perturbation that causes transmembrane flow of K+ out of the adjacent cytoplasm (Fig. 2) generates a transient ion gradient along the length of the hollow core of a microtubule or a potential gradient along the microfilament which forms a wire-like conductor for ion flow.