Cytoskeletal proteins in the cell nucleus: a special nuclear actin perspective

Abstract

The emerging role of cytoskeletal proteins in the cell nucleus has become a new frontier in cell biology. Actin and actin-binding proteins regulate chromatin and gene expression, but importantly they are beginning to be essential players in genome organization. These actin-based functions contribute to genome stability and integrity while affecting DNA replication and global transcription patterns. This is likely to occur through interactions of actin with nuclear components including nuclear lamina and subnuclear organelles. An exciting future challenge is to understand how these actin-based genome-wide mechanisms may regulate development and differentiation by interfering with the mechanical properties of the cell nucleus and how regulated actin polymerization plays a role in maintaining nuclear architecture. With a special focus on actin, here we summarize how cytoskeletal proteins operate in the nucleus and how they may be important to consolidate nuclear architecture for sustained gene expression or silencing.

Nuclear myosin 1 activates p21 gene transcription in response to DNA damage through a chromatin-based mechanism

“…ytoskeletal proteins such as actin and myosin have emerged as key factors in the regulation of a dynamic chromatin landscape compatible with active transcription 1 . Actin and a specific isoform of myosin 1c referred to as nuclear myosin 1 (NM1) associate with the genome in both insects and mammals [2][3][4] .…”

Loss of β‐Actin Leads to Accelerated Mineralization and Dysregulation of Osteoblast‐Differentiation Genes during Osteogenic Reprogramming

“…-actin plays essential roles in many cytoplasmic processes, including cell division, vesicle trafficking, and motility, [1,2] and it has recently emerged as a critical player in the nucleus. -actin is involved in chromatin and transcription regulation, [3] regulating both nuclear-encoded mitochondrial and developmental genes, [4][5][6] and plays a role in the dynamic changes in transcriptional patterns that occur during differentiation. [5,6] We recently reported that direct reprogramming of -actin knockout (KO) mouse embryonic fibroblasts (MEFs) to neurons fails to induce the expression of a large portion of neuronal genes in comparison to the wild-type (WT) condition, primarily due to increased heterochromatin levels at transcription start sites of neuronal genes in -actin KO.…”

“…Beyond its wide array of cytoskeletal functions, actin can exert broad-ranging influence over signaling pathways involving cellular differentiation programs through both cytoplasmic and nuclear mechanisms. The cortical actin cytoskeleton provides a scaffold for and can spatially confine signaling complexes, [3,5,[25][26][27] and changes in the relative proportion of actin isoforms alter cell surface features that affect both biophysical properties [28] and TGF-growth factor signaling. [29] Nuclear actin influences transcription and chromatin remodeling, with consequent effects on cellular identity, [30] and can directly affect signaling pathways at the transcriptional level.…”

Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse

“…The role of actin filaments in nuclear biology has been a matter of controversy for much of its history. While a case could be made for the presence of actin monomers in the nucleus due to the presence of specific nuclear import and export components, visualizing actin filaments, or conceptualizing biochemical signals that would drive actin polymerization has been technically challenging (127). Emergence of tools to specifically study actin filaments in the nucleus using specific reporters with nuclear localization signals as well as the presence of filament regulators such as WASp and Arp2/3 in the nucleus have reignited interest in this field.…”