F‐actin Binding Protein, Anillin, Regulates Integrity of Intercellular Junctions in Human Epithelial Cells

Abstract

Tight junctions (TJ) and adherens junctions (AJ) are key morphological features of differentiated epithelial cells that regulate the integrity and permeability of tissue barriers. Structure and remodeling of epithelial junctions depends on their interactions with the underlying actomyosin cytoskeleton. Anillin is a unique scaffolding protein interacting with different cytoskeletal components, including actin filaments and myosin motors. Its role in the regulation of mammalian epithelial junctions remains unexplored. Downregulation of anillin expression in human prostate and lung epithelial cells triggered disassembly of AJ and TJ without altering the expression of junctional proteins. This junctional disassembly was accompanied by dramatic disorganization of the perijunctional actomyosin belt; while the general architecture of the actin cytoskeleton and activation of non‐muscle myosin II remained unchanged. Furthermore, loss of anillin disrupted the adducin‐spectrin membrane skeleton at the areas of cell‐cell contact, selectively decreased γ‐adducin mRNA and protein expression, and induced cytoplasmic aggregation of αII‐spectrin. Down‐regulation of γ‐adducin mimicked the effects of anillin knockdown on epithelial junction integrity. These findings suggest a novel role for anillin in regulating TJ and AJ in human epithelia by controlling assembly of the perijunctional actomyosin cytoskeleton and the membrane skeleton. This work was supported by NIH grants DK083968 and DK084953 to A.I.I.

Anillin governs mitotic rounding during early epidermal development

“…Our study identifies ANLN as a major regulator of the actin cytoskeleton and epidermal morphogenesis. In keeping with previous reports [31,[34][35][36], we demonstrate that ANLN is essential for AJ organization in the developing epidermis and defects in the actin cytoskeleton can also explain abnormalities in apicobasal polarity and BM assembly [15], which are all major regulators of epidermal morphogenesis [3,80]. Moreover, we uncover an early, novel function for ANLN in mitotic rounding and its dependent processes: chromosome segregation, spindle orientation, and mitotic progression (Fig.…”

“…Because ANLN was recently shown to function in adherens junctions (AJs) [34,36], and because we detected ANLN also in epidermal junctions (Fig. 1A, B), we asked whether ANLN deficiency affects AJ organization.…”

“…ANLN has a well-established role in cell division, with its loss of function resulting in cytokinesis failure and multinucleation of many cell types [review in [27,28,32,33]]. In non-mitotic epithelial cells, ANLN was shown to be essential for cell-cell adhesion in a variety of cultured human epithelial cells [34] and in the developing Xenopus [35,36]. ANLN also plays a role in the migration of cultured human epithelial cells [37] and in ventral enclosure in the developing C. elegans [38].…”

Stress vesicles are induced by acute mechanical force and precede the commitment of epidermal stem cells to terminal differentiation

“…Mechanosensitive ion channel, such as TRP (Transient Receptor Potential) and Piezo are additional potent transducers of physical information to the cell. Their activation in response to tensile forces applied to the cell membrane allows calcium to pass across a gradient into the cytoplasm activating signaling cascades that influence cell adhesion and keratinocyte differentiation 90,91 . Piezo1, a family member of the mechanosensitive cation channels, which is also expressed in epidermal keratinocytes, has previously been implicated in mediating keratinocyte mechanical sensitivity and migration during wound healing 92,93 .…”

Early zygotic gene product Dunk interacts with anillin to regulate Myosin II during Drosophila cleavage

“…The lack of obvious phenotype in initial myosin recruitment upon disruption of anillin may be due to functional redundancy, as suggested by studies in cultured cells (Piekny and Glotzer, 2008). In addition to a critical function in cytokinesis, recent studies have also revealed anillin’s function in regulating myosin localization at the cell-cell junctions (Wang et al, 2015) and organizing medial-apical actomyosin network in non-dividing epithelial cells (Arnold et al, 2019). Interestingly, a recent study suggests that anillin may function as an unconventional RhoA effector that feeds back and boosts RhoA’s activity by kinetically increasing its residence time at PI(4,5)P 2 -enriched membrane (Budnar et al, 2019).…”