Structure, Regulation, and Functional Diversity of Microvilli on the Apical Domain of Epithelial Cells

Sauvanet, Cécile; Wayt, Jessica; Pelaseyed, Thaher; Bretscher, Anthony

doi:10.1146/annurev-cellbio-100814-125234

Cited by 151 publications

(169 citation statements)

References 235 publications

(285 reference statements)

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“…3C, arrows), consistent with actin filaments that are typically found in microvilli lining the luminal space in epithelial tissues. However, unlike typical microvilli, which given a certain cell type adopt a consistent shape and length within the same cell (Sauvanet et al, 2015), we found membrane protrusions of various lengths, some of which were branched, further indicating that their architecture could be more complex.…”

Section: Membrane Protrusions In the Intercellular Space Form An Extecontrasting

confidence: 55%

Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

Jorgens

Inman

Wojcik

et al. 2016

Journal of Cell Science

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The importance of context in regulation of gene expression is now an accepted principle; yet the mechanism by which the microenvironment communicates with the nucleus and chromatin in healthy tissues is poorly understood. A functional role for nuclear and cytoskeletal architecture is suggested by the phenotypic differences observed between epithelial and mesenchymal cells. Capitalizing on recent advances in cryogenic techniques, volume electron microscopy and super-resolution light microscopy, we studied human mammary epithelial cells in three-dimensional (3D) cultures forming growtharrested acini. Intriguingly, we found deep nuclear invaginations and tunnels traversing the nucleus, encasing cytoskeletal actin and/or intermediate filaments, which connect to the outer nuclear envelope. The cytoskeleton is also connected both to other cells through desmosome adhesion complexes and to the extracellular matrix through hemidesmosomes. This finding supports a physical and/or mechanical link from the desmosomes and hemidesmosomes to the nucleus, which had previously been hypothesized but now is visualized for the first time. These unique structures, including the nuclear invaginations and the cytoskeletal connectivity to the cell nucleus, are consistent with a dynamic reciprocity between the nucleus and the outside of epithelial cells and tissues.

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Section: Membrane Protrusions In the Intercellular Space Form An Extecontrasting

confidence: 55%

Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

Jorgens

Inman

Wojcik

et al. 2016

Journal of Cell Science

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“…5), which are convoluted apical membrane extensions with cores of crosslinked actin bundles. Microvilli are also found in other polarized epithelia and excellent reviews on microvillar biology are available (Crawley et al, 2014;Sauvanet et al, 2015). Here, we focus on the intestinal phenotypes of relevant mouse models and human conditions in which microvillus structure is perturbed.…”

Section: Formation Of the Microvillar Brush Bordermentioning

confidence: 99%

“…Here, we focus on the intestinal phenotypes of relevant mouse models and human conditions in which microvillus structure is perturbed. Microvillus formation begins when actin filaments nucleate at electron-dense plaques in the apical actin terminal web (Crawley et al, 2014;Sauvanet et al, 2015). The actin-bundling protein villin is first expressed at E10 and becomes apically concentrated by E13.5 (Ezzell et al, 1989) where it crosslinks and stabilizes actin fibers.…”

Section: Formation Of the Microvillar Brush Bordermentioning

confidence: 99%

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Generation of intestinal surface: an absorbing tale

et al. 2016

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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.

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“…Microvilli line the apical surface of epithelial cells forming a densely packed structure known as the brush border in tube-like tissues, such as intestines, kidney, and lung (2)(3)(4)(5). The best known function of microvilli is to massively increase membrane surface area of these tissues to promote solute exchange, although these protrusions may also allow cells to communicate with their extracellular surroundings (6).…”

mentioning

confidence: 99%

Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins

Weck

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Unconventional myosin 7a (Myo7a), myosin 7b (Myo7b), and myosin 15a (Myo15a) all contain MyTH4-FERM domains (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in their cargo binding tails and are essential for the growth and function of microvilli and stereocilia. Numerous mutations have been identified in the MyTH4-FERM tandems of these myosins in patients suffering visual and hearing impairment. Although a number of MF domain binding partners have been identified, the molecular basis of interactions with the C-terminal MF domain (CMF) of these myosins remains poorly understood. Here we report the high-resolution crystal structure of Myo7b CMF in complex with the extended PDZ3 domain of USH1C (a.k.a., Harmonin), revealing a previously uncharacterized interaction mode both for MyTH4-FERM tandems and for PDZ domains. We predicted, based on the structure of the Myo7b CMF/USH1C PDZ3 complex, and verified that Myo7a CMF also binds to USH1C PDZ3 using a similar mode. The structure of the Myo7b CMF/USH1C PDZ complex provides mechanistic explanations for >20 deafness-causing mutations in Myo7a CMF. Taken together, these findings suggest that binding to PDZ domains, such as those from USH1C, PDZD7, and Whirlin, is a common property of CMFs of Myo7a, Myo7b, and Myo15a.M icrovilli and stereocilia are both actin bundle-based, fingerlike protrusions found on apical surfaces of many epithelial cells (1). Microvilli line the apical surface of epithelial cells forming a densely packed structure known as the brush border in tube-like tissues, such as intestines, kidney, and lung (2-5). The best known function of microvilli is to massively increase membrane surface area of these tissues to promote solute exchange, although these protrusions may also allow cells to communicate with their extracellular surroundings (6). Stereocilia, on the other hand, are composed of several rows of protrusions with graded height forming a staircase-like structure on the apical surface of inner ear hair cells, which collectively function to sense sound waves (7,8). Despite clear morphological and functional differences, microvilli and stereocilia share certain features at the molecular level. For example, the packing and organization of microvilli and stereocilia both rely on homologous cadherin-based tip-link complexes that target to the distal ends of these protrusions (9, 10). Additionally, a set of homologous unconventional myosins-including Myo1, Myo3, Myo6, and Myo7-are shared by and critical for the development, maintenance, and functions of microvilli and stereocilia (1,11,12).This study focuses on Myo7b, an unconventional myosin enriched in the microvilli of transporting epithelial cells (11, 13). Myo7b is characterized by a pair of MyTH4-FERM tandems in its tail cargo-binding domain. In addition to Myo7b, Myo7a, Myo10, and Myo15a also contain one or two MyTH4-FERM tandems in their tail domains (14). A common property of MyTH4-FERM myosins is their involvement in the formation or elongation/stabilization of actin-bundle support...

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Structure, Regulation, and Functional Diversity of Microvilli on the Apical Domain of Epithelial Cells

Cited by 151 publications

References 235 publications

Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

Generation of intestinal surface: an absorbing tale

Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins

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