The presence of atypical cytoskeletal dynamics, structures, and associated morphologies is a common theme uniting numerous diseases and developmental disorders. In particular, cytoskeletal dysregulation is a common cellular feature of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. While the numerous activators and inhibitors of dysregulation present complexities for characterizing these elements as byproducts or initiators of the disease state, it is increasingly clear that a better understanding of these anomalies is critical for advancing the state of knowledge and plan of therapeutic attack. In this review, we focus on the hallmarks of cytoskeletal dysregulation that are associated with cofilin-linked actin regulation, with a particular emphasis on the formation, monitoring, and inhibition of cofilin-actin rods. We also review actin-associated proteins other than cofilin with links to cytoskeleton-associated neurodegenerative processes, recognizing that cofilin-actin rods comprise one strand of a vast web of interactions that occur as a result of cytoskeletal dysregulation. Our aim is to present a current perspective on cytoskeletal dysregulation, connecting recent developments in our understanding with emerging strategies for biosensing and biomimicry that will help shape future directions of the field.

No abstract

No abstract

BAR (Bin, Amphiphysin and Rvs) protein domains are responsible for the generation of membrane curvature and represent a critical mechanical component of cellular functions. Thus, BAR domains have great potential as components of membrane-remodeling tools for cell biologists. In this work, we describe the design and implementation of a family of versatile light-gated I-BAR domain containing tools (CRY-BARs) with applications in the remodeling of membrane architectures and the control of cellular dynamics. By taking advantage of the intrinsic membrane binding propensity of the I-BAR domain, CRY-BARs can be used for spatial and temporal control of cellular processes that require induction of membrane protrusions. Using cell lines and primary neuron cultures, we demonstrate that the CRY-BAR optogenetic tool reports membrane dynamic changes associated with cellular activity. Moreover, we provide evidence that Ezrin acts as a relay between the plasma membrane and the actin cytoskeleton and therefore is an important mediator of switch function. Overall, CRY-BARs hold promise as a useful addition to the optogenetic toolkit to study membrane remodeling in live cells.

BAR (Bin, Amphiphysin and Rvs) protein domains are responsible for the generation of membrane curvature and represent a critical mechanical component of cellular function. Thus, BAR domains have great potential as components of membrane‐remodeling tools for cell biologists. In this work, we describe the design and implementation of a versatile light‐gated I‐BAR domain containing tool (‘CRY‐BAR’) with applications in the remodeling of membrane architectures and the control of cellular dynamics. By taking advantage of the intrinsic membrane association of the I‐BAR domain, CRY‐BAR can be used for spatial and temporal control of cellular dynamics and the initiation of cellular protrusions. CRY‐BAR function is demonstrated in immortalized and primary cell lines; Ezrin, which acts as a relay between the plasma membrane and the actin cytoskeleton, is implicated as an important mediator of switch function. Overall, CRY‐BAR holds promise as a widely applicable addition to the optogenetic toolkit.