Genomes and Genes
Gene Symbol: pins
Description: partner of inscuteable
Alias: CG5692, Dmel\CG5692, PINS, Pins, Rad, Raps, rad, raps, rapsyn, partner of inscuteable, CG5692-PA, partner of inscutable, pins-PA, rapsinoid, rapsynoid
Species: fruit fly
- Segalen M, Johnston C, Martin C, Dumortier J, Prehoda K, David N, et al. The Fz-Dsh planar cell polarity pathway induces oriented cell division via Mud/NuMA in Drosophila and zebrafish. Dev Cell. 2010;19:740-52 pubmed publisher..Overall, we describe a Frizzled-Dishevelled-NuMA pathway that orients division from Drosophila to vertebrates. ..
- Kaltschmidt J, Brand A. Asymmetric cell division: microtubule dynamics and spindle asymmetry. J Cell Sci. 2002;115:2257-64 pubmed..In this commentary we discuss recent findings on how the mitotic spindle is positioned and on cleavage site induction and place them in the context of cell size asymmetry in different model organisms. ..
- Lee C, Robinson K, Doe C. Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature. 2006;439:594-8 pubmed..Clonal analysis in larval brains showed that pins mutant neuroblasts rapidly fail to self-renew, whereas lethal giant larvae (lgl) mutant neuroblasts generate ..
- Doe C, Bowerman B. Asymmetric cell division: fly neuroblast meets worm zygote. Curr Opin Cell Biol. 2001;13:68-75 pubmed..Mammalian epithelia also use this complex to regulate apical/basal polarity. Recent results have allowed us to compare the mechanisms regulating asymmetric cell division in Drosophila neuroblasts and the C. elegans zygote. ..
- Yu F, Ong C, Chia W, Yang X. Membrane targeting and asymmetric localization of Drosophila partner of inscuteable are discrete steps controlled by distinct regions of the protein. Mol Cell Biol. 2002;22:4230-40 pubmed..A complex of apically localized proteins, including Inscuteable (Insc), Partner of Inscuteable (Pins), Bazooka (Baz), DmPar-6, DaPKC, and G alpha i, is required to mediate and coordinate basal protein ..
- Chia W, Yang X. Asymmetric division of Drosophila neural progenitors. Curr Opin Genet Dev. 2002;12:459-64 pubmed..Recent findings also suggest possible mechanisms by which the processes of cell-cycle progression, neuronal lineage development and asymmetric divisions may be integrated. ..
- Cai Y, Yu F, Lin S, Chia W, Yang X. Apical complex genes control mitotic spindle geometry and relative size of daughter cells in Drosophila neuroblast and pI asymmetric divisions. Cell. 2003;112:51-62 pubmed..mitotic spindle geometry and unequal daughter cell size are controlled by two parallel pathways (Bazooka/DaPKC and Pins/G alpha i) within the apical complex...
- Bergstralh D, Haack T, St Johnston D. Epithelial polarity and spindle orientation: intersecting pathways. Philos Trans R Soc Lond B Biol Sci. 2013;368:20130291 pubmed publisher..Work in the past 20 years has defined a core ternary complex consisting of Pins, Mud and GÎ±i that participates in spindle orientation in both asymmetric and symmetric divisions...
- Wee B, Johnston C, Prehoda K, Doe C. Canoe binds RanGTP to promote Pins(TPR)/Mud-mediated spindle orientation. J Cell Biol. 2011;195:369-76 pubmed publisher..We show that a previously uncharacterized portion of Canoe directly binds the Partner of Inscuteable (Pins) tetratricopeptide repeat (TPR) domain...
- Guilgur L, Prudêncio P, Ferreira T, Pimenta Marques A, Martinho R. Drosophila aPKC is required for mitotic spindle orientation during symmetric division of epithelial cells. Development. 2012;139:503-13 pubmed publisher..We showed that Drosophila aPKC is required in vivo for spindle planar orientation and apical exclusion of Pins (Raps)...
- Kopein D, Katanaev V. Drosophila GoLoco-protein Pins is a target of Galpha(o)-mediated G protein-coupled receptor signaling. Mol Biol Cell. 2009;20:3865-77 pubmed publisher..Here we demonstrate that the poly-GoLoco-containing protein Pins of Drosophila can bind to both GDP- and GTP-forms of Drosophila Galpha(o)...
- Wang H, Ng K, Qian H, Siderovski D, Chia W, Yu F. Ric-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins. Nat Cell Biol. 2005;7:1091-8 pubmed..Ric-8 is necessary for membrane targeting of Galphai, Pins and Gbeta13F, presumably by regulating multiple Galpha subunit(s)...
- Yu F, Wang H, Qian H, Kaushik R, Bownes M, Yang X, et al. Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. Genes Dev. 2005;19:1341-53 pubmed..Simultaneous removal of the two GoLoco motif proteins, Loco and Pins, results in defects that are essentially indistinguishable from those observed in Gbeta13F or Ggamma1 mutants, ..
- Parmentier M, Woods D, Greig S, Phan P, Radovic A, Bryant P, et al. Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila. J Neurosci. 2000;20:RC84 pubmed..Here, we describe a new Drosophila protein, Rapsynoid (Raps), which interacts in a two-hybrid assay with the signal transduction protein Galpha(i)...
- Siegrist S, Doe C. Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell. 2005;123:1323-35 pubmed..We show that astral microtubules, kinesin Khc-73, and Discs large (Dlg) induce cortical polarization of Pins/Galphai in Drosophila neuroblasts; this cortical domain is functional for generating spindle asymmetry, daughter-..
- Rolls M, Albertson R, Shih H, Lee C, Doe C. Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol. 2003;163:1089-98 pubmed..and Lgl, and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation...
- Fuse N, Hisata K, Katzen A, Matsuzaki F. Heterotrimeric G proteins regulate daughter cell size asymmetry in Drosophila neuroblast divisions. Curr Biol. 2003;13:947-54 pubmed..Furthermore, the multiple equal cleavages of G beta mutant neuroblasts accompany neural defects; this finding suggests indispensable roles of eccentric division in assuring the stem cell properties of neuroblasts. ..
- Lee C, Andersen R, Cabernard C, Manning L, Tran K, Lanskey M, et al. Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev. 2006;20:3464-74 pubmed..We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal. ..
- Le Borgne R, Schweisguth F. Unequal segregation of Neuralized biases Notch activation during asymmetric cell division. Dev Cell. 2003;5:139-48 pubmed..We propose that coordinated upregulation of ligand activity by Neuralized and inhibition of receptor activity by Numb results in a robust bias in Notch signaling. ..
- Ohno S. Intercellular junctions and cellular polarity: the PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity. Curr Opin Cell Biol. 2001;13:641-8 pubmed..Recent studies on the role of this PAR-aPKC complex in epithelial cell polarization provide new insights into the molecular basis of epithelial junctional formation and cell polarity. ..
- David N, Martin C, Segalen M, Rosenfeld F, Schweisguth F, Bellaiche Y. Drosophila Ric-8 regulates Galphai cortical localization to promote Galphai-dependent planar orientation of the mitotic spindle during asymmetric cell division. Nat Cell Biol. 2005;7:1083-90 pubmed..antero-posterior axis by Frizzled signalling and, during this division, activation of Galphai depends on Partner of Inscuteable (Pins)...
- Yoshiura S, Ohta N, Matsuzaki F. Tre1 GPCR signaling orients stem cell divisions in the Drosophila central nervous system. Dev Cell. 2012;22:79-91 pubmed publisher..The GPCR Tre1 activates the G protein o? subunit in neuroblasts by interacting with the epithelium to recruit Pins, which regulates spindle orientation...
- Cabernard C, Doe C. Apical/basal spindle orientation is required for neuroblast homeostasis and neuronal differentiation in Drosophila. Dev Cell. 2009;17:134-41 pubmed publisher..We conclude that the ratio of apical/basal determinants specifies neuroblast/GMC identity, and that apical/basal spindle orientation is required for neuroblast homeostasis and neuronal differentiation. ..
- Caussinus E, Gonzalez C. Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet. 2005;37:1125-9 pubmed..We found that larval brain tissue carrying neuroblasts with mutations in raps (also called pins), mira, numb or pros grew to more than 100 times their initial size, invading other tissues and ..
- Izumi Y, Ohta N, Itoh Furuya A, Fuse N, Matsuzaki F. Differential functions of G protein and Baz-aPKC signaling pathways in Drosophila neuroblast asymmetric division. J Cell Biol. 2004;164:729-38 pubmed..Further analysis of Gbetagamma and other mutants indicates a predominant role of Partner of Inscuteable-Galphai in spindle orientation...
- Doe C. Cell polarity: the PARty expands. Nat Cell Biol. 2001;3:E7-9 pubmed..This common cell-polarity mechanism is used in cell-specific ways, as highlighted by the recent finding that at least two different types of asymmetric division are observed in Drosophila neural precursors. ..
- Lee C, Wilkinson B, Siegrist S, Wharton R, Doe C. Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell. 2006;10:441-9 pubmed..Single neuroblast clones lacking Prospero have a similar phenotype. We conclude that Brat suppresses neuroblast stem cell self-renewal and promotes neuronal differentiation. ..
- Ahringer J. Control of cell polarity and mitotic spindle positioning in animal cells. Curr Opin Cell Biol. 2003;15:73-81 pubmed..Microtubules and conserved PAR proteins are essential mediators of cell polarity, and mitotic spindle positioning depends on heterotrimeric G protein signalling and the microtubule motor protein dynein. ..
- Langevin J, Le Borgne R, Rosenfeld F, Gho M, Schweisguth F, Bellaiche Y. Lethal giant larvae controls the localization of notch-signaling regulators numb, neuralized, and Sanpodo in Drosophila sensory-organ precursor cells. Curr Biol. 2005;15:955-62 pubmed..Thus, Lgl regulates cell fate by controlling Pon cortical localization, asymmetric localization of Numb and Neuralized, and plasma-membrane localization of Sandopo. ..
- Yu F, Morin X, Cai Y, Yang X, Chia W. Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell. 2000;100:399-409 pubmed..We show here that Partner of Inscuteable (Pins), a new component of asymmetric divisions, is required for Inscuteable to asymmetrically localize...
- Cabernard C, Prehoda K, Doe C. A spindle-independent cleavage furrow positioning pathway. Nature. 2010;467:91-4 pubmed publisher..proteins (Pavarotti, Anillin, and Myosin) are localized to the neuroblast basal cortex at anaphase onset by a Pins cortical polarity pathway, and can induce a basally displaced furrow even in the complete absence of a mitotic ..
- Johnston C, Hirono K, Prehoda K, Doe C. Identification of an Aurora-A/PinsLINKER/Dlg spindle orientation pathway using induced cell polarity in S2 cells. Cell. 2009;138:1150-63 pubmed publisher..to construct cortical polarity in a normally unpolarized cell line and use this method to characterize Partner of Inscuteable (Pins; LGN/AGS3 in mammals) -dependent spindle orientation...
- Nipper R, Siller K, Smith N, Doe C, Prehoda K. Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts. Proc Natl Acad Sci U S A. 2007;104:14306-11 pubmed..Neuroblasts asymmetrically localize Galphai, Pins, and Mud proteins; Pins/Galphai direct cortical polarity, whereas Mud is required for spindle orientation...
- Bellaiche Y, Beaudoin Massiani O, Stuttem I, Schweisguth F. The planar cell polarity protein Strabismus promotes Pins anterior localization during asymmetric division of sensory organ precursor cells in Drosophila. Development. 2004;131:469-78 pubmed..At mitosis, Stbm forms an anterior crescent that overlaps with the distribution of Partner of Inscuteable (Pins) and Discs-large (Dlg), two components of the anterior Dlg-Pins-Galphai complex that regulates the ..
- Peng C, Manning L, Albertson R, Doe C. The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature. 2000;408:596-600 pubmed..We conclude that Dlg and Lgl promote, and myosin II inhibits, actomyosin-dependent basal protein targeting in neuroblasts. ..
- Smith C, Lau K, Rahmani Z, Dho S, Brothers G, She Y, et al. aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J. 2007;26:468-80 pubmed..These results suggest a model in which phosphorylation of Numb by aPKC regulates its polarized distribution in epithelial cells as well as during asymmetric cell divisions. ..
- Rebollo E, Sampaio P, Januschke J, Llamazares S, Varmark H, Gonzalez C. Functionally unequal centrosomes drive spindle orientation in asymmetrically dividing Drosophila neural stem cells. Dev Cell. 2007;12:467-74 pubmed..Apical aster maintenance requires the function of Pins. These results reveal that spindle orientation in Drosophila larval NBs is determined very early in the cell cycle, ..
- Bellaiche Y, Radovic A, Woods D, Hough C, Parmentier M, O Kane C, et al. The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila. Cell. 2001;106:355-66 pubmed..The Discs-large (Dlg) and Partner of Inscuteable (Pins) proteins accumulate at the anterior cortex, while Bazooka (Baz) relocalizes to the posterior cortex...
- Schaefer M, Shevchenko A, Knoblich J. A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr Biol. 2000;10:353-62 pubmed..A novel 70 kDa protein called Partner of Inscuteable (Pins) and a heterotrimeric G-protein alpha subunit were found to bind specifically to the functional ..
- Izumi Y, Ohta N, Hisata K, Raabe T, Matsuzaki F. Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nat Cell Biol. 2006;8:586-93 pubmed..Receptor-independent G-protein signalling involving the GoLoco protein Pins is essential for spindle orientation in both cell types...
- Speicher S, Fischer A, Knoblich J, Carmena A. The PDZ protein Canoe regulates the asymmetric division of Drosophila neuroblasts and muscle progenitors. Curr Biol. 2008;18:831-7 pubmed publisher..Here, we show that Cno functions as a new effector of the apical proteins Inscuteable (Insc)-Partner of Inscuteable (Pins)-Galphai during the asymmetric division of Drosophila neuroblasts (NBs)...
- Andersen R, Turnbull D, Johnson E, Doe C. Sgt1 acts via an LKB1/AMPK pathway to establish cortical polarity in larval neuroblasts. Dev Biol. 2012;363:258-65 pubmed publisher..Double mutants lacking Sgt1 and Pins (a microtubule-induced polarity pathway component) resulted in neuroblasts without detectable cortical polarity and ..
- Ahringer J. Playing ping pong with pins: cortical and microtubule-induced polarity. Cell. 2005;123:1184-6 pubmed..In this issue of Cell, it is turned around and shown that the transfer of polarity information between the cortex and the spindle is not just one way. In Drosophila neuroblasts, the spindle also has polarizing activity on the cortex. ..
- Dawes Hoang R, Wieschaus E. Cell and developmental biology--a shared past, an intertwined future. Dev Cell. 2001;1:27-36 pubmed..Our goal in this commentary is to examine the common origin of cell and developmental biology, to explore ways in which they currently interact, and to consider the connections and differences that exist between these two fields. ..
- Rath P, Lin S, Udolph G, Cai Y, Yang X, Chia W. Inscuteable-independent apicobasally oriented asymmetric divisions in the Drosophila embryonic CNS. EMBO Rep. 2002;3:660-5 pubmed..We conclude that inscuteable is not required for all apicobasally oriented asymmetric divisions and that, in some cellular contexts, bazooka can mediate apicobasal asymmetric divisions without inscuteable. ..
- Moorhouse K, Burgess D. How to be at the right place at the right time: the importance of spindle positioning in embryos. Mol Reprod Dev. 2014;81:884-95 pubmed publisher..The data generated from these model organisms have made unique contributions to our knowledge of spindle positioning. Future work will address how all of these different factors work together to regulate the position of the spindle. ..
- Folker E, Schulman V, Baylies M. Muscle length and myonuclear position are independently regulated by distinct Dynein pathways. Development. 2012;139:3827-37 pubmed..muscle development and found that several factors, including Dynein heavy chain, Dynein light chain and Partner of inscuteable, contribute to the regulation of both muscle length and myonuclear positioning...
- Garcia J, Dewey E, Johnston C. Dishevelled binds the Discs large 'Hook' domain to activate GukHolder-dependent spindle positioning in Drosophila. PLoS ONE. 2014;9:e114235 pubmed publisher..Cooperation between these two evolutionarily-conserved cell polarity pathways could have important implications to both the development and maintenance of tissue homeostasis in animals. ..
- Katanaev V, Tomlinson A. Dual roles for the trimeric G protein Go in asymmetric cell division in Drosophila. Proc Natl Acad Sci U S A. 2006;103:6524-9 pubmed..cell's anterior cortex is a key patterning event and is achieved by the combined action of many proteins, including Pins, which itself is localized anteriorly...
- Yu F. Analysis of the roles of Pins and heterotrimeric G proteins in asymmetric division of Drosophila neuroblasts. Methods Enzymol. 2004;389:364-82 pubmed..This article describes methods of analyzing the role of Pins and heterotrimeric G proteins in Drosophila neuroblast asymmetric division.
- Rossi F, Gonzalez C. Synergism between altered cortical polarity and the PI3K/TOR pathway in the suppression of tumour growth. EMBO Rep. 2012;13:157-62 pubmed publisherLoss of function of pins (partner of inscuteable) partially disrupts neuroblast (NB) polarity and asymmetric division, results in fewer and smaller NBs and inhibits Drosophila larval brain growth...
- Yu F, Morin X, Kaushik R, Bahri S, Yang X, Chia W. A mouse homologue of Drosophila pins can asymmetrically localize and substitute for pins function in Drosophila neuroblasts. J Cell Sci. 2003;116:887-96 pubmed..segregation of cell fate determinants requires an apically localized protein complex that includes Inscuteable, Pins, Bazooka, DmPar-6, DaPKC and Galphai. Pins acts to stabilize the apical complex during neuroblast divisions...
- Wang C, Li S, Januschke J, Rossi F, Izumi Y, Garcia Alvarez G, et al. An ana2/ctp/mud complex regulates spindle orientation in Drosophila neuroblasts. Dev Cell. 2011;21:520-33 pubmed publisher..Ana2 and Ctp localize Mud to the centrosomes and cell cortex and facilitate/maintain the association of Mud with Pins at the apical cortex...
- Kurusu M, Maruyama Y, Adachi Y, Okabe M, Suzuki E, Furukubo Tokunaga K. A conserved nuclear receptor, Tailless, is required for efficient proliferation and prolonged maintenance of mushroom body progenitors in the Drosophila brain. Dev Biol. 2009;326:224-36 pubmed publisher..These results as a whole uncover a distinct regulatory mechanism of self-renewal and differentiation of the MB progenitors that is different from the mechanisms found in other progenitors. ..
- Slack C, Overton P, Tuxworth R, Chia W. Asymmetric localisation of Miranda and its cargo proteins during neuroblast division requires the anaphase-promoting complex/cyclosome. Development. 2007;134:3781-7 pubmed..Our results demonstrate that APC/C activity and ubiquitylation of Miranda are required for the asymmetric localisation of Miranda and its cargo proteins to the NB cortex. ..
- Tuxworth R, Chia W. Asymmetric cell division: Miranda chauffeured by Jaguar?. Mol Cell. 2003;11:288-9 pubmed..An intact F-actin cytoskeleton was known to be required, and now a myosin VI (Jaguar) has been shown to be necessary for basal targeting of cell fate determinants in neuroblasts. ..
- Bosveld F, Markova O, Guirao B, Martin C, Wang Z, Pierre A, et al. Epithelial tricellular junctions act as interphase cell shape sensors to orient mitosis. Nature. 2016;530:495-8 pubmed publisher..microtubules and orienting cell division via the Dynein-associated protein Mud independently of the classical Pins/GÎ±i pathway...
- Cate M, Gajendra S, Alsbury S, Raabe T, Tear G, Mitchell K. Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila. Development. 2016;143:972-7 pubmed publisher..These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. ..
- GONCZY P. Mechanisms of spindle positioning: focus on flies and worms. Trends Cell Biol. 2002;12:332-9 pubmed..This article discusses recent findings that indicate how this mechanism might be used for spindle positioning during Drosophila and Caenorhabditis elegans development. ..
- Saini N, Reichert H. Neural stem cells in Drosophila: molecular genetic mechanisms underlying normal neural proliferation and abnormal brain tumor formation. Stem Cells Int. 2012;2012:486169 pubmed publisher..These cellular and molecular findings in Drosophila are likely to provide valuable genetic links for analyzing mammalian neural stem cells and tumor biology. ..
- Knust E. G protein signaling and asymmetric cell division. Cell. 2001;107:125-8 pubmed..Receptor-independent activation of heterotrimeric G proteins by the Drosophila GoLoco protein Partner of Inscuteable seems to represent a novel mechanism to control these events.
- Leevers S. Which way is up?. Trends Genet. 2000;16:434-5 pubmed
- Schweisguth F. Cell polarity: fixing cell polarity with Pins. Curr Biol. 2000;10:R265-7 pubmed..A protein complex is assembled in a step-wise manner at the apical pole of Drosophila neuroblasts. This complex organizes the apical-basal polarity of asymmetrically dividing neuroblasts, and may act via G-protein signalling. ..