Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 176

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Interaction between PAR-3 and the aPKC–PAR-6 complex is indispensable for apical domain development of epithelial cells

Horikoshi, Yosuke, Suzuki, Atsushi, Yamanaka, Tomoyuki, Sasaki, Kazunori, Mizuno, Keiko, Sawada, Hajime, Yonemura, Shigenobu, Ohno, Shigeo·2009·Journal of Cell Science
DOI 10.1242/jcs.043174
Open this paper in CoChat — free account

Abstract

The evolutionarily conserved polarity proteins PAR-3, atypical protein kinase C (aPKC) and PAR-6 critically regulate the apical membrane development required for epithelial organ development. However, the molecular mechanisms underlying their roles remain to be clarified. We demonstrate that PAR-3 knockdown in MDCK cells retards apical protein delivery to the plasma membrane, and eventually leads to mislocalized apical domain formation at intercellular regions in both two-dimensional and three-dimensional culture systems. The defects in PAR-3 knockdown cells are efficiently rescued by wild-type PAR-3, but not by a point mutant (S827/829A) that lacks the ability to interact with aPKC, indicating that formation of the PAR-3–aPKC–PAR-6 complex is essential for apical membrane development. This is in sharp contrast with tight junction maturation, which does not necessarily depend on the aPKC–PAR-3 interaction, and indicates that the two fundamental processes essential for epithelial polarity are differentially regulated by these polarity proteins. Importantly, highly depolarized cells accumulate aPKC and PAR-6, but not PAR-3, on apical protein-containing vacuoles, which become targeted to PAR-3-positive primordial cell-cell contact sites during the initial stage of the repolarization process. Therefore, formation of the PAR-3–aPKC–PAR-6 complex might be required for targeting of not only the aPKC–PAR-6 complex but also of apical protein carrier vesicles to primordial junction structures.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1242/jcs.043174

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 8 references

Research works printed but not linked: 40

  1. Aceto, D., Beers, M. and Kemphues, K. J. (2006). Interaction of PAR-6 with CDC-42 is required for maintenance but not establishment of PAR asymmetry in C. elegans. Dev. Biol.299, 386-397. · DOI
  2. Adachi, M., Inoko, A., Hata, M., Furuse, K., Umeda, K., Itoh, M. and Tsukita, S. (2006). Normal establishment of epithelial tight junctions in mice and cultured cells lacking expression of ZO-3, a tight-junction MAGUK protein. Mol. Cell. Biol.26, 9003-9015. · DOI
  3. Atwood, S. X., Chabu, C., Penkert, R. R., Doe, C. Q. and Prehoda, K. E. (2007). Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC. J. Cell Sci.120, 3200-3206. · DOI · Paper page
  4. Bayless, K. J. and Davis, G. E. (2002). The Cdc42 and Rac1 GTPases are required for capillary lumen formation in three-dimensional extracellular matrices. J. Cell Sci.115, 1123-1136. · DOI · Paper page
  5. Chen, X. and Macara, I. G. (2005). Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat. Cell Biol.7, 262-269. · DOI · Paper page
  6. Folkman, J. and Haudenschild, C. (1980). Angiogenesis in vitro.Nature288, 551-556. · DOI · Paper page
  7. Harris, T. J. and Peifer, M. (2004). Adherens junction-dependent and -independent steps in the establishment of epithelial cell polarity in Drosophila. J. Cell Biol.167, 135-147. · DOI · Paper page
  8. Hirose, T., Izumi, Y., Nagashima, Y., Tamai-Nagai, Y., Kurihara, H., Sakai, T., Suzuki, Y., Yamanaka, T., Suzuki, A., Mizuno, K. et al. (2002). Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. J. Cell Sci.115, 2485-2495. · DOI · Paper page
  9. Hirose, T., Karasawa, M., Sugitani, Y., Fujisawa, M., Akimoto, K., Ohno, S. and Noda, T. (2006). PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains. Development133, 1389-1398. · DOI
  10. Hurd, T. W., Fan, S., Liu, C. J., Kweon, H. K., Hakansson, K. and Margolis, B. (2003a). Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia. Curr. Biol.13, 2082-2090. · DOI
  11. Hurd, T. W., Gao, L., Roh, M. H., Macara, I. G. and Margolis, B. (2003b). Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat. Cell Biol.5, 137-142. · DOI · Paper page
  12. Hutterer, A., Betschinger, J., Petronczki, M. and Knoblich, J. A. (2004). Sequential roles of Cdc42, Par-6, aPKC, and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Dev. Cell6, 845-854. · DOI · Paper page
  13. Izumi, Y., Hirose, T., Tamai, Y., Hirai, S., Nagashima, Y., Fujimoto, T., Tabuse, Y., Kemphues, K. J. and Ohno, S. (1998). An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. J. Cell Biol.143, 95-106. · DOI · Paper page
  14. Kamei, M., Saunders, W. B., Bayless, K. J., Dye, L., Davis, G. E. and Weinstein, B. M. (2006). Endothelial tubes assemble from intracellular vacuoles in vivo.Nature442, 453-456. · DOI · Paper page
  15. Knust, E. and Bossinger, O. (2002). Composition and formation of intercellular junctions in epithelial cells. Science298, 1955-1959. · DOI · Paper page
  16. Lakkaraju, A. and Rodriguez-Boulan, E. (2007). Cell biology: caught in the traffic. Nature448, 266-267. · doi:10.1038/448266a
  17. Louvard, D. (1980). Apical membrane aminopeptidase appears at site of cell-cell contact in cultured kidney epithelial cells. Proc. Natl. Acad. Sci. USA77, 4132-4136. · DOI · Paper page
  18. Martin-Belmonte, F., Gassama, A., Datta, A., Yu, W., Rescher, U., Gerke, V. and Mostov, K. (2007). PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell128, 383-397. · DOI · Paper page
  19. Mishima, A., Suzuki, A., Enaka, M., Hirose, T., Mizuno, K., Ohnishi, T., Mohri, H., Ishigatsubo, Y. and Ohno, S. (2002). Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration in MDCK cells. Genes Cells7, 581-596. · DOI
  20. Mishima, W., Suzuki, A., Yamaji, S., Yoshimi, R., Ueda, A., Kaneko, T., Tanaka, J., Miwa, Y., Ohno, S. and Ishigatsubo, Y. (2004). The first CH domain of affixin activates Cdc42 and Rac1 through alphaPIX, a Cdc42/Rac1-specific guanine nucleotide exchanging factor. Genes Cells9, 193-204. · DOI
  21. Mizuno, K., Suzuki, A., Hirose, T., Kitamura, K., Kutsuzawa, K., Futaki, M., Amano, Y. and Ohno, S. (2003). Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions. J. Biol. Chem.278, 31240-31250. · DOI
  22. Mostov, K. and Martin-Belmonte, F. (2006). Developmental biology: the hole picture. Nature442, 363-364. · DOI
  23. Mostov, K., Su, T. and ter Beest, M. (2003). Polarized epithelial membrane traffic: conservation and plasticity. Nat. Cell Biol.5, 287-293. · DOI · Paper page
  24. Nagai-Tamai, Y., Mizuno, K., Hirose, T., Suzuki, A. and Ohno, S. (2002). Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells. Genes Cells7, 1161-1171. · DOI · Paper page
  25. Nakayama, M., Goto, T. M., Sugimoto, M., Nishimura, T., Shinagawa, T., Ohno, S., Amano, M. and Kaibuchi, K. (2008). Rho-kinase phosphorylates PAR-3 and disrupts PAR complex formation. Dev. Cell14, 205-215. · DOI
  26. Nam, S. C. and Choi, K. W. (2003). Interaction of Par-6 and Crumbs complexes is essential for photoreceptor morphogenesis in Drosophila. Development130, 4363-4372. · DOI
  27. Nishimura, T., Yamaguchi, T., Kato, K., Yoshizawa, M., Nabeshima, Y., Ohno, S., Hoshino, M. and Kaibuchi, K. (2005). PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nat. Cell Biol.7, 270-277. · DOI · Paper page
  28. O'Brien, L. E., Jou, T. S., Pollack, A. L., Zhang, Q., Hansen, S. H., Yurchenco, P. and Mostov, K. E. (2001). Rac1 orientates epithelial apical polarity through effects on basolateral laminin assembly. Nat. Cell Biol.3, 831-838. · DOI · Paper page
  29. Straight, S. W., Shin, K., Fogg, V. C., Fan, S., Liu, C. J., Roh, M. and Margolis, B. (2004). Loss of PALS1 expression leads to tight junction and polarity defects. Mol. Biol. Cell15, 1981-1990. · DOI · Paper page
  30. Suzuki, A. and Ohno, S. (2006). The PAR-aPKC system: lessons in polarity. J. Cell Sci.119, 979-987. · DOI · Paper page
  31. Suzuki, A., Yamanaka, T., Hirose, T., Manabe, N., Mizuno, K., Shimizu, M., Akimoto, K., Izumi, Y., Ohnishi, T. and Ohno, S. (2001). Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. J. Cell Biol.152, 1183-1196. · DOI · Paper page
  32. Suzuki, A., Hirata, M., Kamimura, K., Maniwa, R., Yamanaka, T., Mizuno, K., Kishikawa, M., Hirose, H., Amano, Y., Izumi, N. et al. (2004). aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity. Curr. Biol.14, 1425-1435. · DOI · Paper page
  33. Tanentzapf, G. and Tepass, U. (2003). Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat. Cell Biol.5, 46-52. · DOI · Paper page
  34. Vega-Salas, D. E., Salas, P. J. and Rodriguez-Boulan, E. (1987). Modulation of the expression of an apical plasma membrane protein of Madin-Darby canine kidney epithelial cells: cell-cell interactions control the appearance of a novel intracellular storage compartment. J. Cell Biol.104, 1249-1259. · DOI
  35. Vega-Salas, D. E., Salas, P. J. and Rodriguez-Boulan, E. (1988). Exocytosis of vacuolar apical compartment (VAC): a cell-cell contact controlled mechanism for the establishment of the apical plasma membrane domain in epithelial cells. J. Cell Biol.107, 1717-1728. · DOI
  36. Vogelmann, R. and Nelson, W. J. (2005). Fractionation of the epithelial apical junctional complex: reassessment of protein distributions in different substructures. Mol. Biol. Cell16, 701-716. · DOI
  37. Wu, H., Feng, W., Chen, J., Chan, L. N., Huang, S. and Zhang, M. (2007). PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol. Cell28, 886-898. · DOI · Paper page
  38. Yamanaka, T., Horikoshi, Y., Sugiyama, Y., Ishiyama, C., Suzuki, A., Hirose, T., Iwamatsu, A., Shinohara, A. and Ohno, S. (2003). Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr. Biol.13, 734-743. · DOI · Paper page
  39. Yamanaka, T., Horikoshi, Y., Izumi, N., Suzuki, A., Mizuno, K. and Ohno, S. (2006). Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity. J. Cell Sci.119, 2107-2118. · DOI
  40. Yeaman, C., Grindstaff, K. K. and Nelson, W. J. (1999). New perspectives on mechanisms involved in generating epithelial cell polarity. Physiol. Rev.79, 73-98. · DOI · Paper page

Cited by

See all 176

Metadata

Authors
Horikoshi, Y., Suzuki, A., Yamanaka, T., Sasaki, K., Mizuno, K., Sawada, H., Yonemura, S., & Ohno, S.
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2009-05-15
Volume
122
Issue
10
Pages
1595-1606
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.043174
OpenAlex
W1965410387
Cited by
176
References
8
FWCI
5.40
Type
journal article
Language
en
Open access
closed

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Interaction between PAR-3 and the aPKC–PAR-6 complex is indispensable for apical domain development of epithelial cells. https://app.cochat.ai/papers/10.1242/jcs.043174
The paper
Horikoshi, Y., Suzuki, A., Yamanaka, T., Sasaki, K., Mizuno, K., Sawada, H., Yonemura, S., & Ohno, S. (2009). Interaction between PAR-3 and the aPKC–PAR-6 complex is indispensable for apical domain development of epithelial cells. Journal of Cell Science. https://doi.org/10.1242/jcs.043174

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.