Microtubule polarities indicate that nucleation and capture of microtubules occurs at cell surfaces in Drosophila.

Mogensen, Mette; Tucker, John B.; Stebbings, Howard

doi:10.1083/jcb.108.4.1445

Cited by 98 publications

(50 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In living cells, the microtubule minus-ends are stabilized by binding to specific molecules or structures, such as the γ-tubulin ring complex located at the centrosome (2). In epithelial cells, however, most microtubules do not emanate from the centrosome; instead, they are aligned along the apicobasal axis with their minus ends facing toward the apical domain (3)(4)(5). These observations suggest the presence of unidentified mechanisms that stabilize the minus ends of microtubules at apical regions.…”

mentioning

confidence: 69%

CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells

Toya¹,

Kobayashi²,

Kawasaki³

et al. 2015

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

129

171

View full text Add to dashboard Cite

Polarized epithelial cells exhibit a characteristic array of microtubules that are oriented along the apicobasal axis of the cells. The minus-ends of these microtubules face apically, and the plus-ends face toward the basal side. The mechanisms underlying this epithelial-specific microtubule assembly remain unresolved, however. Here, using mouse intestinal cells and human Caco-2 cells, we show that the microtubule minus-end binding protein CAMSAP3 (calmodulin-regulated–spectrin-associated protein 3) plays a pivotal role in orienting the apical-to-basal polarity of microtubules in epithelial cells. In these cells, CAMSAP3 accumulated at the apical cortices, and tethered the longitudinal microtubules to these sites. Camsap3 mutation or depletion resulted in a random orientation of these microtubules; concomitantly, the stereotypic positioning of the nucleus and Golgi apparatus was perturbed. In contrast, the integrity of the plasma membrane was hardly affected, although its structural stability was decreased. Further analysis revealed that the CC1 domain of CAMSAP3 is crucial for its apical localization, and that forced mislocalization of CAMSAP3 disturbs the epithelial architecture. These findings demonstrate that apically localized CAMSAP3 determines the proper orientation of microtubules, and in turn that of organelles, in mature mammalian epithelial cells.

show abstract

mentioning

confidence: 69%

CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells

Toya¹,

Kobayashi²,

Kawasaki³

et al. 2015

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

129

171

View full text Add to dashboard Cite

show abstract

“…The MT arrangement in the follicle cells is typical of a polarised epithelium, with the minus ends associated with the apical membrane, and the plus ends at the basal side of the cell (Gonzalez et al, 1998;Mogensen, 1999;Mogensen et al, 1989). The arrangement of minus ends appears to be largely unchanged in par-1 mutant cells, but a marker for the plus ends, Kin:β-gal, accumulates in the centre rather than the basal region of the cell.…”

Section: Discussionmentioning

confidence: 99%

“…In epithelial cells, most MTs exhibit a uniform apicobasal polarity, with their minus ends localised at the apical membrane and their plus ends extending towards the basal membrane (Bacallao et al, 1989;Bre et al, 1990;Mogensen et al, 1989). This is also the case in epithelial follicle cells and can be visualised using motor proteins as markers for the plus and minus ends of MTs (Clark et al, 1997).…”

Section: Par-1 Regulates the Density Stability And Polarity Of Mtsmentioning

confidence: 99%

The role of PAR-1 in regulating the polarised microtubule cytoskeleton in theDrosophilafollicular epithelium

et al. 2003

View full text Add to dashboard Cite

The PAR-1 kinase plays a conserved role in cell polarity in C. elegans, Drosophila and mammals. We have investigated the role of PAR-1 in epithelial polarity by generating null mutant clones in the Drosophila follicular epithelium. Large clones show defects in apicobasal membrane polarity, but small clones induced later in development usually have a normal membrane polarity. However, all cells that lack PAR-1 accumulate spectrin and F-actin laterally, and show a strong increase in the density of microtubules. This is consistent with the observation that the mammalian PAR-1 homologues, the MARKs, dramatically reduce the number of microtubules, when overexpressed in tissue culture cells. The MARKs have been proposed to destabilize microtubules by inhibiting the stabilizing activity of the Tau family of microtubuleassociated proteins. This is not the case in Drosophila, however, as null mutations in the single tau family member in the genome have no effect on the microtubule organisation in the follicle cells. Furthermore, PAR-1 activity stabilises microtubules, as microtubules in mutant cells depolymerise much more rapidly after cold or colcemid treatments. Loss of PAR-1 also disrupts the basal localisation of the microtubule plus ends, which are mislocalised to the centre of mutant cells. Thus, Drosophila PAR-1 regulates the density, stability and apicobasal organisation of microtubules. Although the direct targets of PAR-1 are unknown, we suggest that it functions by regulating the plus ends, possibly by capping them at the basal cortex. which were originally identified because they are required for the anterior-posterior polarity of the C. elegans zygote (Kemphues et al., 1988). Three of these proteins, PAR-3, atypical Protein Kinase C (aPKC) and PAR-6, form a conserved protein complex that localises to the anterior cortex of the one cell zygote, where they are required for the asymmetry of the first cell division (Etemad-Moghadam et al., 1995;Hung and Kemphues, 1999;Tabuse et al., 1998;Watts et al., 1996). The Drosophila homologues of PAR-3 (Bazooka), PAR-6 and aPKC localise to a sub-apical region in epithelial cells to define the position of the most apical junction, the zonula adherens, and loss of any of these proteins leads to a loss of polarity (Kuchinke et al., 1998;Muller and Wieschaus, 1996;Petronczki and Knoblich, 2001;Wodarz et al., 2000). The complex shows a similar localisation to the most apical junction in mammalian epithelia, in this case the tight junction, and overexpression of kinase-dead aPKC disrupts the localisation of the tight junction proteins and causes the mislocalisation of apical membrane proteins Suzuki et al., 2001).The conserved serine/threonine kinase PAR-1 has also been implicated in cell polarity in several contexts (Böhm et al., 1997; Guo and Kemphues, 1995;Shulman et al., 2000;Tomancak et al., 2000). PAR-1 localises to the posterior of the C. elegans zygote in a complementary pattern to the PAR-3/PAR-6/aPKC complex, and is required for the asymmetric positioning of the mito...

show abstract

“…The subcellular distribution of microtubules in simple epithelia is completely different from that of actin. MTs are distributed throughout the cytoplasm in a parallel array, with the minus-ends at the submembrane apical region [15,16] (Fig. 1B).…”

Section: Actin and Tubulinmentioning

confidence: 99%

Intermediate filaments: A role in epithelial polarity

Oriolo

Wald

Palau

et al. 2007

Experimental Cell Research

View full text Add to dashboard Cite

Intermediate filaments have long been considered mechanical components of the cell that provide resistance to deformation stress. Practical experimental problems, including insolubility, lack of good pharmacological antagonists, and the paucity of powerful genetic models, have handicapped the research of other functions. In single-layered epithelial cells, keratin intermediate filaments are cortical, either apically polarized or apico-lateral. This review analyzes phenotypes of genetic manipulations of simple epithelial cell keratins in mice and C. elegans that strongly suggest a role of keratins in apico-basal polarization and membrane traffic. Published evidence that intermediate filaments can act as scaffolds for proteins involved in membrane traffic and signaling is also discussed. Such a scaffolding function would generate a highly polarized compartment within the cytoplasm of simple epithelial cells. While in most cases mechanistic explanations for the keratinnull or overexpression phenotypes are still missing, it is hoped investigators will be encouraged to study these as yet poorly understood functions of intermediate filaments.

show abstract

Microtubule polarities indicate that nucleation and capture of microtubules occurs at cell surfaces in Drosophila.

Cited by 98 publications

References 34 publications

CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells

CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells

The role of PAR-1 in regulating the polarised microtubule cytoskeleton in theDrosophilafollicular epithelium

Intermediate filaments: A role in epithelial polarity

Contact Info

Product

Resources

About