Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor

Abstract

BackgroundThere is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear.Presentation of the hypothesisIn the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell. This activity depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme, this binding may occur if the enzyme is either active or inactive but not both. This enzyme-binding is further proposed to stabilize microtubules and microfilaments and to alter rates of GTP and ATP hydrolysis and their levels.Testing the hypothesisEvidence consistent with the cytoskeletal integrative sensor hypothesis is presented in the case of glycolysis. Several testable predictions are made. There should be a relationship between post-translational modifications of tubulin and of actin and their interaction with metabolic enzymes. Different conditions of cytoskeletal dynamics and enzyme-cytoskeleton binding should reveal significant differences in local and perhaps global levels and ratios of ATP and GTP. The different functions of moonlighting enzymes should depend on cytoskeletal binding.Implications of the hypothesisThe physical and chemical effects arising from metabolic sensing by the cytoskeleton would have major consequences on cell shape, dynamics and cell cycle progression. The hypothesis provides a framework that helps the significance of the enzyme-decorated cytoskeleton be determined.

Modeling of sensing potency of cytoskeletal systems decorated with metabolic enzymes

“…The objective of the studies presented in this paper was to provide a quantitative description of the cytoskeletal integrative sensor hypothesis presented previously (Norris et al, 2013). According to this hypothesis, the cytoskeleton senses and integrates the general metabolic activity of the cell which depends on the binding to the cytoskeleton of enzymes and, depending on the nature of the enzyme; this binding may occur if the enzyme is either active or inactive but not both.…”

“…The sensing potency of the cytoskeleton is the capacity of the enzyme-decorated cytoskeleton to transduce the information about the metabolic state of the cell into cytoskeletal dynamics (Norris et al, 2013). The MODEL coupled describes the coupling of the two processes at the system level -tubulin assembly/disassembly and metabolism -due to the binding of a single enzyme of the pathway, E 2 , to tubulin species.…”

“…All these data led us to propose an integrative and regulatory role for microtubules in the metabolism of cells (Norris et al, 2013). In this hypothesis, the cytoskeleton senses and integrates the metabolic activity of the cells so as to meet the challenge of generating a single phenotype that must be coherent with various internal and external conditions (Ovádi and Norris, 2014).…”

The theater management model of plant memory

“…9 Such metabolic sensing would put the enzyme-decorated cytoskeleton in a strong position to be a central player in memory. In higher plant cells, MAPs play a major role in the dynamics of the MT network 43 and the association of certain enzymes with the cytoskeleton contributes to these dynamics.…”

“…8 Given the activitydependent interaction of enzymes with the cytoskeleton, the concept of FDSs (which is scale-free) can be taken further to include the enzyme-decorated cytoskeleton as a metabolic sensor. 9 Here, we bring together ideas about FDSs and competitive coherence in a new, unifying, approach to plant memory. We discuss both concepts in the framework of the metaphor of a theater as previously used in the case of an influential model of consciousness.…”