Anillin: The First Proofreading‐like Scaffold?

Abstract

Scaffolds are fundamental to many cellular signaling pathways. In this essay, a novel class of scaffolds are proposed, whose action bears striking resemblance to kinetic proofreading. Commonly, scaffold proteins are thought to work as tethers, bringing different components of a pathway together to improve the likelihood of their interaction. However, recent studies show that the cytoskeletal scaffold, anillin, supports contractile signaling by a novel, non-tethering mechanism that controls the membrane dissociation kinetics of RhoA. More generally, such proofreading like scaffolds are distinguished from tethers by a rare type of cooperativity, manifest as a super-linear relationship between scaffold concentration and signaling efficiency. The evidence for this hypothesis is reviewed, its conceptual ramifications are considered, and research questions for the future are discussed.

Animal Cell Cytokinesis: The Rho-Dependent Actomyosin-Anilloseptin Contractile Ring as a Membrane Microdomain Gathering, Compressing, and Sorting Machine

“…A recent series of creative experiments using engineered chimeric proteins expressed at cell junctions and cleavage furrows of MCF-7 cells, has led Yap and colleagues to propose that the human Anillin AH domain is required to promote actomyosin activity by cyclically “resetting” Rho-GTP at the membrane, dynamically binding and releasing it, thereby prolonging its cortical residency in a manner that promotes activation of effectors for actomyosin assembly ( Budnar et al, 2019 ; Munro, 2019 ; Morris et al, 2020 ). However, some aspects of that model appear incongruous with ours.…”

Two Septin Complexes Mediate Actin Dynamics During Cell Wound Repair

“…Anillin binds to both actin and Septins and is thought to crosslink them [57][58][59][60][61][62][63][64][65] . Anillin has been shown to promote the compaction of the diffuse Septin meshwork into well-organized rings at the actomyosin ring during cytokinesis 43,61,64,[66][67][68][69] . Therefore, we analyzed whether Anillin is recruited to cell wounds using embryos expressing a GFP-tagged version of Anillin along with an actin reporter (sStMCA; see Methods) (Fig.…”

Comprehensive bioinformatics analysis reveals the prognostic value, predictive value, and immunological roles of ANLN in human cancers

“…The former domain binds RhoA, and the latter is crucial for Anillin recruitment to the equatorial membrane ( Kim et al, 2017 ). ANLN regulates cell contractility through binding to GTP-RhoA, F-actin, activated non-muscle Myosin II (NMII), and other cytoskeletal regulators, like mDia1 and septins ( Morris et al, 2020 ). Apart from its previously described function as organizing and stabilizing actomyosin contractile rings in cytokinesis, recent studies have unveiled its important role in maintaining cell-cell junctions and integrity, as well as regulating cell migration, through adjusting the distribution of Rho-GTP and stabilizing actin filaments, respectively ( Reyes et al, 2014 ; Tian et al, 2015 ).…”

“…Apart from its previously described function as organizing and stabilizing actomyosin contractile rings in cytokinesis, recent studies have unveiled its important role in maintaining cell-cell junctions and integrity, as well as regulating cell migration, through adjusting the distribution of Rho-GTP and stabilizing actin filaments, respectively ( Reyes et al, 2014 ; Tian et al, 2015 ). In addition, ANLN also functions as a scaffolding molecule to promote cellular interactions and signaling pathways ( Morris et al, 2020 ). The localization of ANLN in the cell cycle is not constant.…”