Mechanisms of actin-binding proteins in glycolysis-cytoskeleton coupling

The spatiotemporal coordination between actin cytoskeleton dynamics and glycolytic metabolism represents a critical frontier at the intersection of mechanobiology and cellular metabolism. While a bidirectional relationship between these processes is increasingly recognized, the underlying mechanistic coupling-particularly the role of actin-binding proteins (ABPs)-remains incompletely understood. This knowledge gap significantly limits our comprehensive understanding of mechano-metabolic cross-regulation.

Here, we synthesize recent advancements in cytoskeletal dynamics and metabolic regulation to propose an ABP-mediated "metabolism-cytoskeleton" bidirectional coupling axis as a conceptual framework. By delineating the signaling cascades within this framework, we critically examine how ABPs function as key mediators that coordinate cytoskeletal remodeling with glycolytic flux in specific cellular contexts. Furthermore, we highlight recent mechanistic insights, evaluate prevailing controversies, and identify unresolved scientific questions that warrant future investigation.

The proposed bidirectional "metabolism-cytoskeleton" feedback model conceptualizes the continuum from extracellular mechanotransduction to terminal cellular behavior. By expanding upon traditional unidirectional models, this framework provides a conceptual scaffold for understanding mechano-metabolic crosstalk. Additionally, it explores potential context-dependent therapeutic implications for diseases characterized by aberrant cytoskeletal and metabolic states, such as specific models of cancer and fibrosis.