Pard3

Summary

Gene Symbol: Pard3
Description: par-3 family cell polarity regulator
Alias: Par3, partitioning defective 3 homolog, ASBP, ASIP, PARD-3, atypical PKC isotype-specific-interacting protein, atypical PKC-specific binding protein, par-3 (partitioning defective 3) homolog, three-PDZ containing protein similar to C. elegans PAR3 (partitioning defect)
Species: rat
Products:     Pard3

Top Publications

  1. Hirose T, Izumi Y, Nagashima Y, Tamai Nagai Y, Kurihara H, Sakai T, et al. Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction formation. J Cell Sci. 2002;115:2485-95 pubmed
    The mammalian protein ASIP/PAR-3 interacts with atypical protein kinase C isotypes (aPKC) and shows overall sequence similarity to the invertebrate proteins C...
  2. Ishiuchi T, Takeichi M. Willin and Par3 cooperatively regulate epithelial apical constriction through aPKC-mediated ROCK phosphorylation. Nat Cell Biol. 2011;13:860-6 pubmed publisher
    ..Here, we report that Willin (a FERM-domain protein) and Par3 (a polarity-regulating protein) cooperatively regulate ROCK-dependent apical constriction...
  3. Izumi Y, Hirose T, Tamai Y, Hirai S, Nagashima Y, Fujimoto T, et al. 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. 1998;143:95-106 pubmed
    ..In the present study we report the identification of a protein, ASIP (atypical PKC isotype-specific interacting protein), that binds to aPKCs, and show that it colocalizes with ..
  4. Nishimura T, Yamaguchi T, Kato K, Yoshizawa M, Nabeshima Y, Ohno S, et al. PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nat Cell Biol. 2005;7:270-7 pubmed
    ..We propose that the PAR-6-PAR-3 complex mediates Cdc42-induced Rac activation by means of STEF/Tiam1, and that this process seems to be required for the establishment of neuronal polarity. ..
  5. Ebnet K, Suzuki A, Horikoshi Y, Hirose T, Meyer Zu Brickwedde M, Ohno S, et al. The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J. 2001;20:3738-48 pubmed
    ..Recently, vertebrate orthologues of two of these proteins, ASIP/PAR-3 and PAR-6, were found to form a signalling complex with the small GTPases Cdc42/Rac1 and with atypical ..
  6. Nakayama M, Nakayama A, van Lessen M, Yamamoto H, Hoffmann S, Drexler H, et al. Spatial regulation of VEGF receptor endocytosis in angiogenesis. Nat Cell Biol. 2013;15:249-60 pubmed publisher
    ..Our work uncovers how vessel growth is dynamically controlled by local VEGF receptor endocytosis and the activity of cell polarity proteins. ..
  7. Duncan F, Moss S, Schultz R, Williams C. PAR-3 defines a central subdomain of the cortical actin cap in mouse eggs. Dev Biol. 2005;280:38-47 pubmed
    ..This cortical PAR-3 localization depends on intact microfilaments. These results suggest a role for PAR-3 in establishing asymmetry in the egg and in defining the future site of polar body emission. ..
  8. Zhang H, Macara I. The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis. Nat Cell Biol. 2006;8:227-37 pubmed
    ..Thus, a balance of PAR-3 and TIAM1 is essential to modulate Rac-GTP levels and to allow spine morphogenesis. ..
  9. Beirowski B, Gustin J, Armour S, Yamamoto H, Viader A, North B, et al. Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. Proc Natl Acad Sci U S A. 2011;108:E952-61 pubmed publisher
    ..These results demonstrate that Sirt2 controls an essential polarity pathway in SCs during myelin assembly and provide insights into the association between intracellular metabolism and SC plasticity. ..

More Information

Publications36

  1. Hengst U, Deglincerti A, Kim H, Jeon N, Jaffrey S. Axonal elongation triggered by stimulus-induced local translation of a polarity complex protein. Nat Cell Biol. 2009;11:1024-30 pubmed publisher
    ..We found that the PAR complex, like local translation, is required for stimulated, but not basal, outgrowth. Par3 mRNA is localized to developing axons, and NGF and netrin-1 trigger its local translation...
  2. Feng W, Wu H, Chan L, Zhang M. The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization. EMBO J. 2007;26:2786-96 pubmed
  3. Zhang Y, Wang W, Chen J, Zhang K, Gao F, Gao B, et al. Structural insights into the intrinsic self-assembly of Par-3 N-terminal domain. Structure. 2013;21:997-1006 pubmed publisher
    ..This work unequivocally provides the structural basis for Par-3 NTD self-association and characterizes one type of protein domain that can self-assemble via electrostatic interactions. ..
  4. Feng W, Wu H, Chan L, Zhang M. Par-3-mediated junctional localization of the lipid phosphatase PTEN is required for cell polarity establishment. J Biol Chem. 2008;283:23440-9 pubmed publisher
    ..These results, together with earlier data, firmly establish that Par-3 functions as a scaffold in integrating phosphoinositide signaling events during cellular polarization. ..
  5. Manabe N, Hirai S, Imai F, Nakanishi H, Takai Y, Ohno S. Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells. Dev Dyn. 2002;225:61-9 pubmed
    ..Here, we explore the localization of atypical PKC isotype-specific interacting protein (ASIP), a mammalian homologue of the Caenorhabditis elegans polarity protein PAR-3, in embryonic neural tissues...
  6. Sasaki K, Kakuwa T, Akimoto K, Koga H, Ohno S. Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin-Gαi3 signaling. J Cell Sci. 2015;128:2244-58 pubmed publisher
    ..Taken together, our findings suggest that transcriptional upregulation of Girdin expression and Girdin-Gαi3 signaling play crucial roles in regulating epithelial apicobasal polarity through the PAR complex. ..
  7. Wu H, Feng W, Chen J, Chan L, Huang S, Zhang M. PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol Cell. 2007;28:886-98 pubmed
    ..The concatenation of the PIP-binding PDZ2 and the lipid phosphatase PTEN-binding PDZ3 endows Par-3 as an ideal scaffold protein for integrating PIP signaling events during cellular polarization. ..
  8. Rosso S, Bollati F, Bisbal M, Peretti D, Sumi T, Nakamura T, et al. LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. Mol Biol Cell. 2004;15:3433-49 pubmed
    ..Transfection of wild-type LIMK1 accelerates axon formation and enhances the accumulation of Par3/Par6, insulin-like growth factor (IGF)1 receptors, and neural cell adhesion molecule (NCAM) at growth cones, while ..
  9. Takekuni K, Ikeda W, Fujito T, Morimoto K, Takeuchi M, Monden M, et al. Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule nectin at neuroepithelial cells of developing mouse. J Biol Chem. 2003;278:5497-500 pubmed
    ..These results indicate that nectin-1 and -3 are involved in the localization of PAR-3 at AJs in the neuroepithelial cells of the embryonic telencephalon. ..
  10. Chan J, Jolicoeur C, Yamauchi J, Elliott J, Fawcett J, Ng B, et al. The polarity protein Par-3 directly interacts with p75NTR to regulate myelination. Science. 2006;314:832-6 pubmed
    ..Together, these results point to a critical role in the establishment of cell polarity for myelination. ..
  11. Mizuno K, Suzuki A, Hirose T, Kitamura K, Kutsuzawa K, Futaki M, et al. Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions. J Biol Chem. 2003;278:31240-50 pubmed
    ..These results support the notion that the CR1-mediated self-association of the PAR-3-containing protein complex plays a role during the formation of functional tight junctions. ..
  12. Wong E, Mruk D, Lee W, Cheng C. Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and blood-testis barrier restructuring during spermatogenesis. Proc Natl Acad Sci U S A. 2008;105:9657-62 pubmed publisher
    The Par3/Par6/aPKC and the CRB3/Pals1/PATJ polarity complexes are involved in regulating apical ectoplasmic specialization (ES) and blood-testis barrier (BTB) restructuring in the testis. Par6 was a component of the apical ES and the BTB...
  13. Ikenouchi J, Umeda M. FRMD4A regulates epithelial polarity by connecting Arf6 activation with the PAR complex. Proc Natl Acad Sci U S A. 2010;107:748-53 pubmed publisher
    ..We propose that the Par-3/FRMD4A/cytohesin-1 complex ensures accurate activation of Arf6, a central player in actin cytoskeleton dynamics and membrane trafficking, during junctional remodeling and epithelial polarization. ..
  14. Horikoshi Y, Hamada S, Ohno S, Suetsugu S. Phosphoinositide binding by par-3 involved in par-3 localization. Cell Struct Funct. 2011;36:97-102 pubmed
    ..These data suggested that the putative phospholipid binding by par-3 is important for its localization at cell-cell junctions. ..
  15. Funahashi Y, Namba T, Fujisue S, Itoh N, Nakamuta S, Kato K, et al. ERK2-mediated phosphorylation of Par3 regulates neuronal polarization. J Neurosci. 2013;33:13270-85 pubmed publisher
    ..We previously found that Partition-defective 3 (Par3) is associated with KIF3A (kinesin-2) and is transported into the nascent axon in a KIF3A-dependent fashion...
  16. Tep C, Kim M, Opincariu L, Limpert A, Chan J, Appel B, et al. Brain-derived neurotrophic factor (BDNF) induces polarized signaling of small GTPase (Rac1) protein at the onset of Schwann cell myelination through partitioning-defective 3 (Par3) protein. J Biol Chem. 2012;287:1600-8 pubmed publisher
    Brain-derived neurotrophic factor (BDNF) was shown to play a role in Schwann cell myelination by recruiting Par3 to the axon-glial interface, but the underlying mechanism has remained unclear...
  17. Lampugnani M, Orsenigo F, Rudini N, Maddaluno L, Boulday G, Chapon F, et al. CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci. 2010;123:1073-80 pubmed publisher
    ..VEC co-distributes with members of the Par polarity complex (Par3 and PKCzeta) and is needed for activation of PKCzeta...
  18. Lalli G. RalA and the exocyst complex influence neuronal polarity through PAR-3 and aPKC. J Cell Sci. 2009;122:1499-506 pubmed publisher
    ..Thus, neuronal polarization involves a RalA-regulated association between mediators of vesicle trafficking (exocyst complex) and cell polarity (PAR-3). ..
  19. Nakajima H, Tanoue T. Lulu2 regulates the circumferential actomyosin tensile system in epithelial cells through p114RhoGEF. J Cell Biol. 2011;195:245-61 pubmed publisher
    ..These findings therefore reveal a novel molecular system regulating the circumferential actomyosin belt in epithelial cells...
  20. Schmoranzer J, Fawcett J, Segura M, Tan S, Vallee R, Pawson T, et al. Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration. Curr Biol. 2009;19:1065-74 pubmed publisher
    ..In a search for factors that function with dynein in centrosome orientation, we found that the polarity protein Par3 associated with dynein and that knockdown of Par3 inhibited centrosome orientation by disrupting the position of ..
  21. Wang X, Nie J, Zhou Q, Liu W, Zhu F, Chen W, et al. Downregulation of Par-3 expression and disruption of Par complex integrity by TGF-beta during the process of epithelial to mesenchymal transition in rat proximal epithelial cells. Biochim Biophys Acta. 2008;1782:51-9 pubmed
    ..These data indicate that downregulation of Par-3 and subsequent disruption of Par complex integrity might be one mechanism that TGF-beta destroys cell polarity during EMT. ..
  22. Shi S, Cheng T, Jan L, Jan Y. APC and GSK-3beta are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity. Curr Biol. 2004;14:2025-32 pubmed
  23. Johansson A, Driessens M, Aspenstrom P. The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. J Cell Sci. 2000;113 ( Pt 18):3267-75 pubmed
    ..These findings, together with the reported roles of PAR-6 and PAR-3 in C. elegans, suggest that Cdc42 and Rac1 and PAR-6/PAR-3 are involved in the establishment of cell polarity in epithelial cells. ..
  24. Khazaei M, Püschel A. Phosphorylation of the par polarity complex protein Par3 at serine 962 is mediated by aurora a and regulates its function in neuronal polarity. J Biol Chem. 2009;284:33571-9 pubmed publisher
    ..Aurora A interacts directly with the atypical protein kinase C binding domain of Par3 and phosphorylates it at serine 962...
  25. Ishiuchi T, Takeichi M. Nectins localize Willin to cell-cell junctions. Genes Cells. 2012;17:387-97 pubmed publisher
    ..We recently showed that Willin localizes at the apical junctional complex (AJC) in epithelial cells together with Par3 and regulates the contractility of the circumferential actomyosin cables by recruiting aPKC to the AJC...
  26. Xu G, Wang R, Wang Z, Lei Q, Yu Z, Liu C, et al. NGL-2 Is a New Partner of PAR Complex in Axon Differentiation. J Neurosci. 2015;35:7153-64 pubmed publisher
    ..Further study showed that the C terminal of NGL-2 binds to the PDZ domain of PAR6, and NGL-2 interacts with PAR3 and atypical PKCζ (aPKCζ), with PAR6 acting as a bridge or modifier...
  27. Zhou Q, Fan J, Ding X, Peng W, Yu X, Chen Y, et al. TGF-{beta}-induced MiR-491-5p expression promotes Par-3 degradation in rat proximal tubular epithelial cells. J Biol Chem. 2010;285:40019-27 pubmed publisher
    ..Taken together, we conclude that up-regulation of miR-491-5p contributes to TGF-?-regulated Par-3 expression. Our study uncovered a novel mechanism by which TGF-? disrupts cell junction. ..