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and the mechanical strain of theplasma membrane and cellwall (Figure 1).

Undoubtedly, this recent workof Nakayama et al. [9] will influenceour future models and views ondevelopmental and environmentalcontrol of auxin-mediated growth.Previously published reports ofmechanical regulation of development,for example, lateral root formation aftermechanical bending of Arabidopsisroots [18,19], can now be betterexplained by these new insights.Moreover, although the auxin- andPIN-mediated polarity generationsystem is absent in animals,mechanical stress in animal cellsis also known to trigger changes in thecytoskeleton [20]. It is thus possiblethat the proposed differential exo- andendocytosis of polarity componentsin response to membrane tensionis a widespread phenomenon.

References1. Wi�sniewska, J., Xu, J., Seifertova, D.,

Brewer, P.B., R�u�zi�cka, K., Blilou, I.,Rouquie, D., Benkova, E., Scheres, B., andFriml, J. (2006). Polar PIN localization directsauxin flow in plants. Science 312, 883.

2. Vanneste, S., and Friml, J. (2009). Auxin:a trigger for change in plant development. Cell136, 1005–1016.

3. Sauer, M., Balla, J., Luschnig, C.,Wisniewska, J., Reinohl, V., Friml, J., andBenkova, E. (2006). Canalization of auxin flowby Aux/IAA-ARF-dependent feedbackregulation of PIN polarity. Genes Dev. 20,2902–2911.

4. Wabnik, K., Kleine-Vehn, J., Balla, J., Sauer, M.,Naramoto, S., Reinohl, V., Merks, R.M.,Govaerts, W., and Friml, J. (2010). Emergence

of tissue polarization from synergy ofintracellular and extracellular auxin signaling.Mol. Syst. Biol. 6, 447.

5. Lloyd, C., and Chan, J. (2004). Microtubulesand the shape of plants to come. Nat. Rev. Mol.Cell Biol. 5, 13–22.

6. Crowell, E.F., Timpano, H., Desprez, T.,Franssen-Verheijen, T., Emons, A.M., Hofte, H.,and Vernhettes, S. (2011). Differentialregulation of cellulose orientation at the innerand outer face of epidermal cells in theArabidopsis hypocotyl. Plant Cell 23,2592–2605.

7. Hamant, O., Heisler, M.G., Jonsson, H.,Krupinski, P., Uyttewaal, M., Bokov, P.,Corson, F., Sahlin, P., Boudaoud, A.,Meyerowitz, E.M., et al. (2008). Developmentalpatterning by mechanical signals inArabidopsis. Science 322, 1650–1655.

8. Heisler, M.G., Hamant, O., Krupinski, P.,Uyttewaal, M., Ohno, C., Jonsson, H., Traas, J.,and Meyerowitz, E.M. (2010). Alignmentbetween PIN1 polarity and microtubuleorientation in the shoot apical meristemreveals a tight coupling betweenmorphogenesis and auxin transport. PLoS Biol.8, e1000516.

9. Nakayama, N., Smith, R.S., Mandel, T.,Robinson, S., Kimura, S., Boudaoud, A., andKuhlemeier, C. (2012). Mechanical regulationof auxin-mediated growth. Curr. Biol. 22,1468–1476.

10. Grunewald, W., and Friml, J. (2010). The marchof the PINs: developmental plasticity bydynamic polar targeting in plant cells. EMBO J.29, 2700–2714.

11. Paciorek, T., Za�zımalova, E., Ruthardt, N.,Petra�sek, J., Stierhof, Y.-D., Kleine-Vehn, J.,Morris, D.A., Emans, N., Jurgens, G.,Geldner, N., et al. (2005). Auxin inhibitsendocytosis and promotes its own efflux fromcells. Nature 435, 1251–1256.

12. Robert, S.,Kleine-Vehn, J., Barbez,E., Sauer,M.,Paciorek, T., Baster, P., Vanneste, S., Zhang, J.,Simon, S., �Covanova, M., et al. (2010). ABP1mediates auxin inhibition of clathrin-dependentendocytosis in Arabidopsis. Cell 143, 111–121.

13. Xu, T., Wen, M., Nagawa, S., Fu, Y., Chen, J.-G.,Wu, M.-J., Perrot-Rechenmann, C., Friml, J.,Jones, A.M., and Yang, Z. (2010). Cellsurface- and Rho GTPase-based auxinsignaling controls cellular interdigitationin Arabidopsis. Cell 143, 99–110.

14. Chen, X., Naramoto, S., Robert, S., Tejos, R.,Lofke, C., Lin, D., Yang, Z., and Friml, J. (2012).ABP1 and ROP6 GTPase signaling regulateclathrin-mediated endocytosis in Arabidopsisroots. Curr. Biol. 22, 1326–1332.

15. Lin, D., Nagawa, S., Chen, J., Cao, L., Chen, X.,Xu, T., Li, H., Dhonukshe, P., Yamamuro, C.,Friml, J., et al. (2012). A ROPGTPase-dependentauxin signaling pathway regulates thesubcellular distribution of PIN2 in Arabidopsisroots. Curr. Biol. 22, 1319–1325.

16. Feraru, E., Feraru, M.I., Kleine-Vehn, J.,Martiniere, A., Mouille, G., Vanneste, S.,Vernhettes, S., Runions, J., and Friml, J. (2011).PIN polarity maintenance by the cell wall inArabidopsis. Curr. Biol. 21, 338–343.

17. Kleine-Vehn, J., Wabnik, K., Martiniere, A.,qangowski, q., Willig, K., Naramoto, S.,Leitner, J., Tanaka, H., Jakobs, S., Robert, S.,et al. (2011). Recycling, clustering, andendocytosis jointly maintain PIN auxin carrierpolarity at the plasma membrane. Mol. Syst.Biol. 7, 540.

18. Ditengou, F.A., Teale, W.D., Kochersperger, P.,Flittner, K.A., Kneuper, I., van der Graaff, E.,Nziengui, H., Pinosa, F., Li, X., Nitschke, R.,et al. (2008). Mechanical induction of lateral rootinitiation in Arabidopsis thaliana. Proc. Natl.Acad. Sci. USA 105, 18818–18823.

19. Laskowski, M., Grieneisen, V.A., Hofhuis, H.,ten Hove, C.A., Hogeweg, P., Maree, A.F.M.,and Scheres, B. (2008). Root systemarchitecture from coupling cell shape to auxintransport. PLoS Biol. 6, e307.

20. Szarama, K.B., Gavara, N., Petralia, R.S.,Kelley, M.W., and Chadwick, R.S. (2012).Cytoskeletal changes in actin and microtubulesunderlie the developing surface mechanicalproperties of sensory and supporting cells inthe mouse cochlea. Development 139,2187–2197.

Department of Plant Systems Biology, VIB,Technologiepark 927, B-9052 Gent, Belgiumand Department of Plant Biotechnology andBioinformatics, Ghent University,Technologiepark 927, B-9052 Gent, Belgium.E-mail: jifri@psb.vib-ugent.be

http://dx.doi.org/10.1016/j.cub.2012.06.053

Color Vision: Retinal Blues

Two complementary studies have resolved the circuitry underlying green–bluecolor discrimination in the retina. A blue-sensitive interneuron provides theinhibitory signal required for computing green–blue color opponency.

Jamie Johnston, Federico Esposti,and Leon Lagnado

Our ability to detect different colorsrelies on color-sensitive receptorsin the retina, named cones. In primatesthere are three types of cone, sensitiveto either blue, green or red, but in mostother mammals there are only twotypes, blue and green. Despite a limitednumber of cone types, we are able todetect a myriad colors; this is achievedby comparing the response fromdifferent cones. For example, the

response from blue cones is comparedwith that from green cones to givecolors along the blue-green axis.

The cells in the retina performingsuch comparisons are called coloropponent ganglion cells. Ganglion cellsthat compare blue and green light canbe classed as blue-ON/green-OFF,excited by blue but inhibited by greenlight, or they can be classed asgreen-ON/blue-OFF, excited by greenbut inhibited by blue. To understandthe neural circuits by which thesecolor-opponent ganglion cells are built

it is important to realize that conesdo not send visual signals to ganglioncells directly, but through a classof relay neuron called bipolar cells(Figure 1A). Depending on the typeof cone that they receive inputs from,bipolar cells are tuned to be mostsensitive either to blue or green light.Crucially, bipolar cells also fall into twoclasses distinguished by the polarityof their response to an increase in lightintensity. Hence, in the retina one canfind both green-ON and green-OFFbipolar cells, excited by incrementsor decrements in the intensity ofgreen light.There is good evidence that, in

primates, a blue-ON/green-OFFganglion cell is built by pooling inputsfrom both blue-ON and green-OFFbipolar cells [1–3]; this canonical

OFF

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mGluR6AMPA/KainateGlycine

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Current Biology

Figure 1. Blue-green color opponency circuits in the retina.

(A) Graphical depiction of the blue-ON/green-OFF pathway. Green-OFF bipolar cells andblue-ON bipolar cells project in the OFF and ON strata of the retinal inner plexiform layer,respectively (dashed lines). The two cell types make excitatory synapses onto a blue-ON/green-OFF ganglion cell. (B) Graphical depiction of the green-ON/blue-OFF pathway, asdescribed by [4,5]. In this case a blue-ON bipolar cell provides the inhibitory contribution tothe green-ON/blue-OFF ganglion cell through the sign-inverting synapse of the blue-sensitivebipolar cell (B Amacrine). (C) Graphical depiction of the voltage responses to blue and greenlight for the represented cells.

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pathway is shown in Figure 1A. Ifa green-ON/blue-OFF ganglion cellwere built using the same simplestrategy, green-ON and blue-OFFbipolar cells would be required. Theproblem that has been sittinguncomfortably with vision scientistsis that a bipolar cell responding todecrements in blue light, the putativeblue-OFF, has not been identified sofar. The likely reason is revealed in tworecent papers by Sher and DeVries [4]and Chen and Li [5]: the function of theelusive blue-OFF bipolar cell is actuallycarried out by inverting signals fromblue-ON bipolar cells through aninhibitory interneuron, the amacrinecell (Figure 1B). This is a simplesolution, but it is surprising becausethe dogma had been that amacrinecells are not color-selective.

Using multi-electrode arrays, Sherand DeVries [4] recorded the activityof many ganglion cells in retinae of theground squirrel, a popular mammal forstudying color vision. By stimulatingwith blue and green light they identifiedboth blue-ON/green-OFF andgreen-ON/blue-OFF color-opponent

ganglion cells and found that thereceptive fields of both tile the retinain a regular pattern. They theninvestigated the inputs underlyingthese ganglion cell responses, inparticular taking advantage of the factthat the ON bipolar cell pathway isactivated through a metabotropicglutamate receptor, the mGluR6. Byblocking this receptor they showedthat, as expected, the green-ONcomponent of green-ON/blue-OFFganglion cells is abolished. Butparadoxically, the blue-OFF responsealso disappeared, indicating that it alsosomehow originated in ON bipolarcells.

A possible solution to thisconundrum came when Sher andDeVries [4] found that an antagonist ofinhibitory glycinergic receptors alsoabolished the blue-OFF response inganglion cells. In the inner retina thereis a subclass of amacrine interneuronthat inhibits ganglion cells by releasingglycine. Could this type of amacrine cellbe used to build a color-opponentganglion cell? The problem with thissuggestion is that color-sensitive

amacrine cells had never been reportedbefore [6].Cue Chen and Li [5], who used

electrophysiology to demonstrate thatthe retina of ground squirrel doesindeed contain a population ofblue-sensitive amacrine cell. Bylabeling these neurons during theirrecordings, they found that they havea distinct morphology, with dendritesramifying in the same strata of the innerretina as the terminals of blue-ONbipolar cells. Satisfyingly, theseblue-sensitive amacrine cells alsostained positive for glycinetransporters, providing clear evidencethat they provide inhibitory input to thegreen-ON/blue-OFF ganglion cells. Theresulting circuit explaining thegreen-ON/blue-OFF response is shownin Figure 1B,C. A blue-OFF bipolar cellis not needed!

Different Pathways for ColorOpponencyIf amacrine cells can be used togenerate a blue-OFF response inganglion cells, might they also be usedto generate a green-OFF response?This idea seems worth pursuingin ground squirrels, because Sherand DeVries found that antagonistsof the mGluR6 receptor — whichcause a general block of the ONpathway — also blocked green-OFFresponses in blue-ON/green-OFFganglion cells (Figure 2A in [4]). Thus,there may also be a green-sensitiveamacrine cell lurking in the retina ofthis animal. We can postulate that thisamacrine cell would be GABAergicrather than glycinergic, becausestrychnine failed to block thegreen-OFF response [4]. It may evenbe that mammals have evolveddifferent circuits for buildingblue-ON/green-OFF ganglion cells:the simple pathway in Figure 1A inprimates, and an alternative pathwayin which the signal through green-ONbipolar cells is inverted through anamacrine cell, similar to that shownin Figure 1B.Although blue-OFF bipolar cells have

not been identified physiologically(though see [7–9]), absence of evidencedoes not provide evidence for absence.If they do exist, it may be that they playa role in retinal processes other thanclassical color opponency. Forinstance, the retina contains a smallpercentage of ganglion cells thathave an intrinsic sensitivity to lightand very large receptive fields. These

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intrinsically photosensitive ganglioncells also demonstrate blue-OFFresponses generated through cones[10]. Do these signals travel throughblue-sensitive amacrine cells orthrough the elusive blue-OFF bipolarcell? And if there are blue-sensitiveamacrine cells, might there also bered- or green-sensitive amacrine cellsinvolved in red/green colouropponency? The retina continues tosurprise us.

References1. Calkins, D.J., Tsukamoto, Y., and Sterling, P.

(1998). Microcircuitry and mosaic ofa blue-yellow ganglion cell in the primate retina.J. Neurosci. 18, 3373–3385.

2. Dacey, D.M., and Lee, B.B. (1994). The‘blue-on’ opponent pathway in primate retina

originates from a distinct bistratified ganglioncell type. Nature 367, 731–735.

3. Crook, J.D., Davenport, C.M., Peterson, B.B.,Packer, O.S., Detwiler, P.B., and Dacey, D.M.(2009). Parallel ON and OFF cone bipolarinputs establish spatially coextensivereceptive field structure of blue-yellow ganglioncells in primate retina. J. Neurosci. 29,8372–8387.

4. Sher, A., and DeVries, S.H. (2012). Anon-canonical pathway for mammalianblue-green color vision. Nat. Neurosci. 15,952–953.

5. Chen, S., and Li, W. (2012). A color-codingamacrine cell may provide a blue-Off signalin a mammalian retina. Nat. Neurosci. 15,954–956.

6. Calkins, D.J., and Sterling, P. (1996). Absenceof spectrally specific lateral inputs to midgetganglion cells in primate retina. Nature 381,613–615.

7. Klug, K., Herr, S., Ngo, I.T., Sterling, P., andSchein, S. (2003). Macaque retina contains anS-cone OFF midget pathway. J. Neurosci. 23,9881–9887.

8. Liu, P.C., and Chiao, C.C. (2007). Morphologicidentification of the OFF-type blue cone bipolarcell in the rabbit retina. Invest. Ophthalmol. Vis.Sci. 48, 3388–3395.

9. Gouras (1995). Color Vision. In Webvision: TheOrganization of the Retina and Visual System[Internet] (Salt Lake City (UT): University of UtahHealth Sciences Centre).

10. Dacey, D.M., Liao, H.W., Peterson, B.B.,Robinson, F.R., Smith, V.C., Pokorny, J.,Yau, K.W., and Gamlin, P.D. (2005).Melanopsin-expressing ganglion cells inprimate retina signal colour and irradianceand project to the LGN. Nature 433,749–754.

MRC Laboratory of Molecular Biology,Hills Road, Cambridge, CB2 0QH, UK.E-mail: ll1@mrc-lmb.cam.ac.uk

http://dx.doi.org/10.1016/j.cub.2012.07.022

Bacteriophage Tubulins: CarryingTheir Own Cytoskeleton Key

Cytoskeletal elements are well known to be widespread in eukaryotes andprokaryotes, providing important, diverse functions for cells large and small.Two new studies report that some bacteriophages encode their own tubulinhomologs to facilitate phage reproduction within the host cell.

Daniel P. Haeusserand William Margolin

The last decades of research haveuncovered a plenitude of prokaryotichomologs of eukaryotic actin, tubulin,and intermediate filaments in sundryorganisms once thought devoid of anorganized cytoskeleton [1]. To date,the identified prokaryotic tubulinsuper-family members consist of FtsZ,TubZ, and BtubA/B. Although theconservation of their primary sequenceidentity is limited to the GDP/GTP-binding motif (G box), their crystalstructures show remarkable similaritybetween folds [2]. FtsZ is a highlyconserved cell division protein foundin most bacteria, several phyla ofarchaea, chloroplasts, and themitochondria of certain protists [3].TubZ is encoded within low-copynumber plasmids of Bacillus species,where it functions in a plasmidsegregation system. In this system, theTubR protein binds both to TubZ andto tubS centromeric sites on plasmidDNA to facilitate DNA segregation [4].Phylogenetically closest to a/b-tubulin,BtubA/B of Prosthecobacter areunique among bacterial tubulin

homologues in their ability to form largemicrotubule-like structures, but theirbiological role is unknown [5].

The proliferation of metagenomicshas uncovered an additional reservoirof cytoskeletal proteins forcharacterization: bacteriophages.Research over a decade agoidentified a protein, p1, fromBacillus subtilis phage f29 thatpolymerizes into filaments that mayplay a role in anchoring the phagereplication machinery to thecell membrane [6]. This smallcoiled-coil protein polymerizes ina nucleotide-independent manner,but lacks hallmarks of intermediatefilament assembly [7]. More recently,researchers identified a phageactin homolog, Alp6A, in Bacillusthuringiensis phage 0305f8-36 [8].Alp6A forms filaments, but its functionis unknown. Now, two new studies[9,10] show that some bacteriophageencode their own tubulin-likeproteins. Kraemer et al. [9] report thepresence of a family of proteins, namedPhuZ for ‘Phage tubulin/FtsZ’,and characterize a PhuZ froma Pseudomonas chlororaphis phage.Oliva et al. [10] report a protein

structurally similar to TubZ froma phage of Clostridium botulinum thatalso encodes botulism toxin. Each ofthese phage-encoded tubulinhomologs assembles intoGTP-dependent two-strandedhelical filaments, and it is likely thatthey both function to organize phageDNA.Scanning genomic sequence

databases, Kraemer et al. [9] identifiednovel tubulin homologs that clusteredphylogenetically into two distinctgroups. The first of these clusters hasseven members present in differentClostridium species, with four encodedby the chromosome, one by a plasmid,and three by phages. One of thesephages, called c-st, harbors the TubZstudied by Oliva et al. [10]. The secondcluster, PhuZ, has four identifiedmembers, each encoded by a differentPseudomonas phage. Notably, thephage genomes represented in eachof these phylogenetic clusters areunusually large, suggesting thatphages with large genomes maybenefit from encoding their owncytoskeletal protein.The crystal structure of the

monomeric GDP-bound form of PhuZfrom phage 201f2-1 of P. chlororaphiscomprises an amino-terminal domaincontaining the G box, a long helical(H7) bridge domain and a smallcarboxy-terminal domain. Althoughit assembles into two-stranded helicalfilaments like TubZ, PhuZ’s structurelacks a conserved interdomain helix(H6) that is important for thepolymerization of other tubulin