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Cell Jan 2023How SARS-CoV-2 penetrates the airway barrier of mucus and periciliary mucins to infect nasal epithelium remains unclear. Using primary nasal epithelial organoid...
How SARS-CoV-2 penetrates the airway barrier of mucus and periciliary mucins to infect nasal epithelium remains unclear. Using primary nasal epithelial organoid cultures, we found that the virus attaches to motile cilia via the ACE2 receptor. SARS-CoV-2 traverses the mucus layer, using motile cilia as tracks to access the cell body. Depleting cilia blocks infection for SARS-CoV-2 and other respiratory viruses. SARS-CoV-2 progeny attach to airway microvilli 24 h post-infection and trigger formation of apically extended and highly branched microvilli that organize viral egress from the microvilli back into the mucus layer, supporting a model of virus dispersion throughout airway tissue via mucociliary transport. Phosphoproteomics and kinase inhibition reveal that microvillar remodeling is regulated by p21-activated kinases (PAK). Importantly, Omicron variants bind with higher affinity to motile cilia and show accelerated viral entry. Our work suggests that motile cilia, microvilli, and mucociliary-dependent mucus flow are critical for efficient virus replication in nasal epithelia.
Topics: Humans; Cilia; COVID-19; Respiratory System; SARS-CoV-2; Microvilli; Virus Internalization; Epithelial Cells
PubMed: 36580912
DOI: 10.1016/j.cell.2022.11.030 -
FEBS Letters Nov 2020Cilia and microvilli are membrane protrusions that extend from the surface of many different mammalian cell types. Motile cilia or flagella are only found on specialized... (Review)
Review
Cilia and microvilli are membrane protrusions that extend from the surface of many different mammalian cell types. Motile cilia or flagella are only found on specialized cells, where they control cell movement or the generation of fluid flow, whereas immotile primary cilia protrude from the surface of almost every mammalian cell to detect and transduce extracellular signals. Despite these differences, all cilia consist of a microtubule core called the axoneme. Microvilli instead contain bundled linear actin filaments and are mainly localized on epithelial cells, where they modulate the absorption of nutrients. Cilia and microvilli constitute subcellular compartments with distinctive lipid and protein repertoires and specialized functions. Here, we summarize the role of sphingolipids in defining the identity and controlling the function of cilia and microvilli in mammalian cells.
Topics: Animals; Cilia; Humans; Microvilli; Sphingolipids
PubMed: 32415987
DOI: 10.1002/1873-3468.13816 -
The Pan African Medical Journal 2018
Topics: Dehydration; Diarrhea; Humans; Hypernatremia; Infant, Newborn; Infant, Premature; Malabsorption Syndromes; Male; Microvilli; Mucolipidoses
PubMed: 30364420
DOI: 10.11604/pamj.2018.30.109.12330 -
Current Opinion in Cell Biology Feb 2023Microvilli are actin bundle-supported surface protrusions assembled by diverse cell types to mediate biochemical and physical interactions with the external environment.... (Review)
Review
Microvilli are actin bundle-supported surface protrusions assembled by diverse cell types to mediate biochemical and physical interactions with the external environment. Found on the surface of some of the earliest animal cells, primordial microvilli likely contributed to bacterial entrapment and feeding. Although millions of years of evolution have repurposed these protrusions to fulfill diverse roles such as detection of mechanical or visual stimuli in inner ear hair cells or retinal pigmented epithelial cells, respectively, solute uptake remains a key essential function linked to these structures. In this mini review, we offer a brief overview of the composition and structure of epithelial microvilli, highlight recent discoveries on the growth of these protrusions early in differentiation, and point to fundamental questions surrounding microvilli biogenesis that remain open for future studies.
Topics: Animals; Microvilli; Actins
PubMed: 36827850
DOI: 10.1016/j.ceb.2023.102153 -
Current Biology : CB Jun 2021Microvilli are actin-bundle-supported surface protrusions that play essential roles in diverse epithelial functions. To develop our understanding of microvilli...
Microvilli are actin-bundle-supported surface protrusions that play essential roles in diverse epithelial functions. To develop our understanding of microvilli biogenesis, we used live imaging to directly visualize protrusion growth at early stages of epithelial differentiation. Time-lapse data revealed that specific factors, including epidermal growth factor pathway substrate 8 (EPS8) and insulin-receptor tyrosine kinase substrate (IRTKS) (also known as BAIAP2L1), appear in diffraction-limited puncta at the cell surface and mark future sites of microvillus growth. New core actin bundles elongate from these puncta in parallel with the arrival of ezrin and subsequent plasma membrane encapsulation. In addition to de novo growth, we also observed that new microvilli emerge from pre-existing protrusions. Moreover, we found that nascent microvilli can also collapse, characterized first by loss of membrane wrapping and ezrin enrichment, followed by a sharp decrease in distal tip EPS8 and IRTKS levels, and ultimately disassembly of the core actin bundle itself. These studies are the first to offer a temporally resolved microvillus growth mechanism and highlight factors that participate in this process; they also provide important insights on the growth of apical specializations that will likely apply to diverse epithelial contexts.
Topics: Actins; Adaptor Proteins, Signal Transducing; Animals; Cell Line; Cell Membrane; Epithelial Cells; Humans; Microfilament Proteins; Microvilli; Opossums; Swine; Time-Lapse Imaging
PubMed: 33951456
DOI: 10.1016/j.cub.2021.04.012 -
Development (Cambridge, England) Jul 2016The vertebrate small intestine requires an enormous surface area to effectively absorb nutrients from food. Morphological adaptations required to establish this... (Review)
Review
The vertebrate small intestine requires an enormous surface area to effectively absorb nutrients from food. Morphological adaptations required to establish this extensive surface include generation of an extremely long tube and convolution of the absorptive surface of the tube into villi and microvilli. In this Review, we discuss recent findings regarding the morphogenetic and molecular processes required for intestinal tube elongation and surface convolution, examine shared and unique aspects of these processes in different species, relate these processes to known human maladies that compromise absorptive function and highlight important questions for future research.
Topics: Animals; Humans; Intestinal Absorption; Intestines; Microvilli; Models, Biological; Morphogenesis; Signal Transduction
PubMed: 27381224
DOI: 10.1242/dev.135400 -
Cellular and Molecular Gastroenterology... 2021
Topics: Endocytosis; Microvilli; Tight Junction Proteins
PubMed: 33757764
DOI: 10.1016/j.jcmgh.2021.02.012 -
Recent advances in understanding and managing malabsorption: focus on microvillus inclusion disease.F1000Research 2019Microvillus inclusion disease (MVID) is a rare congenital severe malabsorptive and secretory diarrheal disease characterized by blunted or absent microvilli with... (Review)
Review
Microvillus inclusion disease (MVID) is a rare congenital severe malabsorptive and secretory diarrheal disease characterized by blunted or absent microvilli with accumulation of secretory granules and inclusion bodies in enterocytes. The typical clinical presentation of the disease is severe chronic diarrhea that rapidly leads to dehydration and metabolic acidosis. Despite significant advances in our understanding of the causative factors, to date, no curative therapy for MVID and associated diarrhea exists. Prognosis mainly relies on life-long total parenteral nutrition (TPN) and eventual small bowel and/or liver transplantation. Both TPN and intestinal transplantation are challenging and present with many side effects. A breakthrough in the understanding of MVID emanated from seminal findings revealing mutations in as a cause for MVID. During the last decade, many studies have thus utilized cell lines and animal models with knockdown of to closely recapitulate the human disease and investigate potential therapeutic options in disease management. We will review the most recent advances made in the research pertaining to MVID. We will also highlight the tools and models developed that can be utilized for basic and applied research to increase our understanding of MVID and develop novel and effective targeted therapies.
Topics: Animals; Humans; Malabsorption Syndromes; Microvilli; Mucolipidoses; Myosin Heavy Chains; Myosin Type V
PubMed: 31824659
DOI: 10.12688/f1000research.20762.1 -
Disease Models & Mechanisms Jan 2016Congenital diarrheal disorders are rare, often fatal, diseases that are difficult to diagnose (often requiring biopsies) and that manifest in the first few weeks of life... (Review)
Review
Congenital diarrheal disorders are rare, often fatal, diseases that are difficult to diagnose (often requiring biopsies) and that manifest in the first few weeks of life as chronic diarrhea and the malabsorption of nutrients. The etiology of congenital diarrheal disorders is diverse, but several are associated with defects in the predominant intestinal epithelial cell type, enterocytes. These particular congenital diarrheal disorders (CDD(ENT)) include microvillus inclusion disease and congenital tufting enteropathy, and can feature in other diseases, such as hemophagocytic lymphohistiocytosis type 5 and trichohepatoenteric syndrome. Treatment options for most of these disorders are limited and an improved understanding of their molecular bases could help to drive the development of better therapies. Recently, mutations in genes that are involved in normal intestinal epithelial physiology have been associated with different CDD(ENT). Here, we review recent progress in understanding the cellular mechanisms of CDD(ENT). We highlight the potential of animal models and patient-specific stem-cell-based organoid cultures, as well as patient registries, to integrate basic and clinical research, with the aim of clarifying the pathogenesis of CDD(ENT) and expediting the discovery of novel therapeutic strategies.
Topics: Abetalipoproteinemia; Animals; Chylomicrons; Diarrhea; Diarrhea, Infantile; Enterocytes; Facies; Fetal Growth Retardation; Hair Diseases; Heterozygote; Humans; Hypobetalipoproteinemias; Lipids; Mice; Mice, Knockout; Microvilli; Models, Animal; Mutation; Protein Transport; Registries; Stem Cells
PubMed: 26747865
DOI: 10.1242/dmm.022269 -
The Journal of Cell Biology Nov 2014Epithelial cells from diverse tissues, including the enterocytes that line the intestinal tract, remodel their apical surface during differentiation to form a brush... (Review)
Review
Epithelial cells from diverse tissues, including the enterocytes that line the intestinal tract, remodel their apical surface during differentiation to form a brush border: an array of actin-supported membrane protrusions known as microvilli that increases the functional capacity of the tissue. Although our understanding of how epithelial cells assemble, stabilize, and organize apical microvilli is still developing, investigations of the biochemical and physical underpinnings of these processes suggest that cells coordinate cytoskeletal remodeling, membrane-cytoskeleton cross-linking, and extracellular adhesion to shape the apical brush border domain.
Topics: Animals; Cell Differentiation; Cytoskeletal Proteins; Cytoskeleton; Enterocytes; Humans; Intestines; Mice; Microvilli; Myosin Heavy Chains; Myosin Type I
PubMed: 25422372
DOI: 10.1083/jcb.201407015