The Drosophila CD2AP/CIN85 orthologue Cindr regulates junctions and cytoskeleton dynamics during tissue patterning
Open accessAbstract
Developing tissues require cells to undergo intricate processes to shift into appropriate niches. This requires a functional connection between adhesion-mediating events at the cell surface and a cytoskeletal reorganization to permit directed movement. A small number of proteins are proposed to link these processes. Here, we identify one candidate, Cindr, the sole Drosophila melanogaster member of the CD2AP/CIN85 family (this family has been previously implicated in a variety of processes). Using D. melanogaster retina, we demonstrate that Cindr links cell surface junctions (E-cadherin) and adhesion (Roughest) with multiple components of the actin cytoskeleton. Reducing cindr activity leads to defects in local cell movement and, consequently, tissue patterning and cell death. Cindr activity is required for normal localization of Drosophila E-cadherin and Roughest, and we show additional physical and functional links to multiple components of the actin cytoskeleton, including the actin-capping proteins capping protein alpha and capping protein beta. Together, these data demonstrate that Cindr is involved in dynamic cell rearrangement in an emerging epithelium.
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.
Integrity signals
Registry
Cites
Statistics
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CD2AP is involved in cell-cell adhesion, regulates the actin cytoskeleton, and physically interacts with p130CAS (CASS1).
“CD2AP is involved in cell–cell adhesion, regulates the actin cytoskeleton and physically interacts with p130CAS (CASS1) [61, 74].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [61]
The Introduction links CD2AP to adhesion molecules and actin dynamics, supporting the cell–cell adhesion and cytoskeleton portions of the claim. Our copy does not report a physical interaction with p130Cas; p130Cas appears only in a reference title about the two proteins localizing to different F-actin structures. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Usami, Y., Popov, S., & Göttlinger, H. G. (2007) · Journal of Virology · doi:10.1128/jvi.00314-07 · Cited by 143 · see citing works
Flagged first, then by citations
Research works printed but not linked: 59
- Bao, S., and R. Cagan. 2005. Preferential adhesion mediated by Hibris and Roughest regulates morphogenesis and patterning in the Drosophila eye. Dev. Cell. 8: 925–935. 15935781
- Bao, S., and R. Cagan. 2006. Fast cloning inverted repeats for RNA interference. RNA. 12: 2020–2024. 17005926 PMC1624905
- Bogler, O., F.B. Furnari, A. Kindler-Roehrborn, V.W. Sykes, R. Yung, H.J. Huang, and W.K. Cavenee. 2000. SETA: a novel SH3 domain-containing adapter molecule associated with malignancy in astrocytes. Neuro. Oncol. 2: 6–15. 11302255 PMC1920697
- Brand, A.H., and N. Perrimon. 1993. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 118: 401–415. 8223268
- Brett, T.J., L.M. Traub, and D.H. Fremont. 2002. Accessory protein recruitment motifs in clathrin-mediated endocytosis. Structure. 10: 797–809. 12057195
- Bruck, S., T.B. Huber, R.J. Ingham, K. Kim, H. Niederstrasser, P.M. Allen, T. Pawson, J.A. Cooper, and A.S. Shaw. 2006. Identification of a novel inhibitory actin-capping protein binding motif in CD2-associated protein. J. Biol. Chem. 281: 19196–19203. 16707503 PMC2581424
- Chen, B., S.C. Borinstein, J. Gillis, V.W. Sykes, and O. Bogler. 2000. The glioma-associated protein SETA interacts with AIP1/Alix and ALG-2 and modulates apoptosis in astrocytes. J. Biol. Chem. 275: 19275–19281. 10858458
- Cordero, J.B., D.E. Larson, C.R. Craig, R. Hays, and R. Cagan. 2007. Dynamic decapentaplegic signaling regulates patterning and adhesion in the Drosophila pupal retina. Development. 134: 1861–1871. 17428827 PMC2957290
- Cormont, M., I. Meton, M. Mari, P. Monzo, F. Keslair, C. Gaskin, T.E. McGraw, and Y. Le Marchand-Brustel. 2003. CD2AP/CMS regulates endosome morphology and traffic to the degradative pathway through its interaction with Rab4 and c-Cbl. Traffic. 4: 97–112. 12559036
- Delalle, I., C.M. Pfleger, E. Buff, P. Lueras, and I.K. Hariharan. 2005. Mutations in the Drosophila orthologs of the F-actin capping protein alpha- and beta-subunits cause actin accumulation and subsequent retinal degeneration. Genetics. 171: 1757–1765. 16143599 PMC1456101
- Dikic, I. 2003. Mechanisms controlling EGF receptor endocytosis and degradation. Biochem. Soc. Trans. 31: 1178–1181. 14641021
- Dikic, I., and S. Giordano. 2003. Negative receptor signalling. Curr. Opin. Cell Biol. 15: 128–135. 12648667
- Dustin, M.L., M.W. Olszowy, A.D. Holdorf, J. Li, S. Bromley, N. Desai, P. Widder, F. Rosenberger, P.A. van der Merwe, P.M. Allen, and A.S. Shaw. 1998. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell. 94: 667–677. 9741631
- Frank, D.J., R. Hopmann, M. Lenartowska, and K.G. Miller. 2006. Capping protein and the Arp2/3 complex regulate nonbundle actin filament assembly to indirectly control actin bundle positioning during Drosophila melanogaster bristle development. Mol. Biol. Cell. 17: 3930–3939. 16822838 PMC1593168
- Gaidos, G., S. Soni, D.J. Oswald, P.A. Toselli, and K.H. Kirsch. 2007. Structure and function analysis of the CMS/CIN85 protein family identifies actin-bundling properties and heterotypic-complex formation. J. Cell Sci. 120: 2366–2377. 17606992
- Gauthier, N.C., P. Monzo, T. Gonzalez, A. Doye, A. Oldani, P. Gounon, V. Ricci, M. Cormont, and P. Boquet. 2007. Early endosomes associated with dynamic F-actin structures are required for late trafficking of H. pylori VacA toxin. J. Cell Biol. 177: 343–354. 17438076 PMC2064141
- Gout, I., G. Middleton, J. Adu, N.N. Ninkina, L.B. Drobot, V. Filonenko, G. Matsuka, A.M. Davies, M. Waterfield, and V.L. Buchman. 2000. Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein. EMBO J. 19: 4015–4025. 10921882 PMC306608
- Grzeschik, N.A., and E. Knust. 2005. IrreC/rst-mediated cell sorting during Drosophila pupal eye development depends on proper localisation of DE-cadherin. Development. 132: 2035–2045. 15788453
- Guild, G.M., P.S. Connelly, L. Ruggiero, K.A. Vranich, and L.G. Tilney. 2003. Long continuous actin bundles in Drosophila bristles are constructed by overlapping short filaments. J. Cell Biol. 162: 1069–1077. 12975350 PMC2172841
- Hall, A. 2005. Rho GTPases and the control of cell behaviour. Biochem. Soc. Trans. 33: 891–895. 16246005
- Hopmann, R., and K.G. Miller. 2003. A balance of capping protein and profilin functions is required to regulate actin polymerization in Drosophila bristle. Mol. Biol. Cell. 14: 118–128. 12529431 PMC140232
- Hopmann, R., J.A. Cooper, and K.G. Miller. 1996. Actin organization, bristle morphology, and viability are affected by actin capping protein mutations in Drosophila. J. Cell Biol. 133: 1293–1305. 8682865 PMC2120907
- Huber, T.B., and T. Benzing. 2005. The slit diaphragm: a signaling platform to regulate podocyte function. Curr. Opin. Nephrol. Hypertens. 14: 211–216. 15821412
- Hutchings, N.J., N. Clarkson, R. Chalkley, A.N. Barclay, and M.H. Brown. 2003. Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85. J. Biol. Chem. 278: 22396–22403. 12690097
- Isenberg, G., U. Aebi, and T.D. Pollard. 1980. An actin-binding protein from Acanthamoeba regulates actin filament polymerization and interactions. Nature. 288: 455–459. 6893736
- Kirsch, K.H., M.M. Georgescu, T. Shishido, W.Y. Langdon, R.B. Birge, and H. Hanafusa. 2001. The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction. J. Biol. Chem. 276: 4957–4963. 11067845
- Kowanetz, K., J. Terzic, and I. Dikic. 2003. Dab2 links CIN85 with clathrin-mediated receptor internalization. FEBS Lett. 554: 81–87. 14596919
- Kurakin, A.V., S. Wu, and D.E. Bredesen. 2003. Atypical recognition consensus of CIN85/SETA/Ruk SH3 domains revealed by target-assisted iterative screening. J. Biol. Chem. 278: 34102–34109. 12829691
- Larson, D.E., Z. Liberman, and R.L. Cagan. 2008. Cellular behavior in the developing Drosophila pupal retina. Mech. Dev. 125: 223–232. 18166433 PMC2965056
- Lehtonen, S., A. Ora, V.M. Olkkonen, L. Geng, M. Zerial, S. Somlo, and E. Lehtonen. 2000. In vivo interaction of the adapter protein CD2-associated protein with the type 2 polycystic kidney disease protein, polycystin-2. J. Biol. Chem. 275: 32888–32893. 10913159
- Lehtonen, S., F. Zhao, and E. Lehtonen. 2002. CD2-associated protein directly interacts with the actin cytoskeleton. Am. J. Physiol. Renal Physiol. 283: F734–F743. 12217865
- Lehtonen, S., E. Lehtonen, K. Kudlicka, H. Holthofer, and M.G. Farquhar. 2004. Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin. Am. J. Pathol. 165: 923–936. 15331416 PMC1618613
- Lynch, D.K., S.C. Winata, R.J. Lyons, W.E. Hughes, G.M. Lehrbach, V. Wasinger, G. Corthals, S. Cordwell, and R.J. Daly. 2003. A Cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton. J. Biol. Chem. 278: 21805–21813. 12672817
- Mege, R.M., J. Gavard, and M. Lambert. 2006. Regulation of cell-cell junctions by the cytoskeleton. Curr. Opin. Cell Biol. 18: 541–548. 16905303
- Miller, D.T., and R.L. Cagan. 1998. Local induction of patterning and programmed cell death in the developing Drosophila retina. Development. 125: 2327–2335. 9584131
- Monzo, P., N.C. Gauthier, F. Keslair, A. Loubat, C.M. Field, Y. Le Marchand-Brustel, and M. Cormont. 2005. Clues to CD2-associated protein involvement in cytokinesis. Mol. Biol. Cell. 16: 2891–2902. 15800069 PMC1142433
- Mustonen, H., A. Lepisto, S. Lehtonen, E. Lehtonen, P. Puolakkainen, and E. Kivilaakso. 2005. CD2AP contributes to cell migration and adhesion in cultured gastric epithelium. Biochem. Biophys. Res. Commun. 332: 426–432. 15910750
- Palmen, T., S. Lehtonen, A. Ora, D. Kerjaschki, C. Antignac, E. Lehtonen, and H. Holthofer. 2002. Interaction of endogenous nephrin and CD2-associated protein in mouse epithelial M-1 cell line. J. Am. Soc. Nephrol. 13: 1766–1772. 12089372
- Parker, L., S. Gross, and L. Alphey. 2001. Vectors for the expression of tagged proteins in Drosophila. Biotechniques. 31: 1280–1282, 1284, 1286. 11768656
- Patari-Sampo, A., P. Ihalmo, and H. Holthofer. 2006. Molecular basis of the glomerular filtration: nephrin and the emerging protein complex at the podocyte slit diaphragm. Ann. Med. 38: 483–492. 17101539
- Peters, I., I. Tossidou, J. Achenbach, R. Woroniecki, M. Mengel, J.K. Park, M. Paschy, K. de Groot, H. Haller, and M. Schiffer. 2006. IGF-binding protein-3 modulates TGF-beta/BMP-signaling in glomerular podocytes. J. Am. Soc. Nephrol. 17: 1644–1656. 16672319
- Reiter, C., T. Schimansky, Z. Nie, and K.F. Fischbach. 1996. Reorganization of membrane contacts prior to apoptosis in the Drosophila retina: the role of the IrreC-rst protein. Development. 122: 1931–1940. 8674431
- Rigaut, G., A. Shevchenko, B. Rutz, M. Wilm, M. Mann, and B. Seraphin. 1999. A generic protein purification method for protein complex characterization and proteome exploration. Nat. Biotechnol. 17: 1030–1032. 10504710
- Schiffer, M., P. Mundel, A.S. Shaw, and E.P. Bottinger. 2004. A novel role for the adaptor molecule CD2-associated protein in transforming growth factor-beta-induced apoptosis. J. Biol. Chem. 279: 37004–37012. 15213232
- Schiwek, D., N. Endlich, L. Holzman, H. Holthofer, W. Kriz, and K. Endlich. 2004. Stable expression of nephrin and localization to cell-cell contacts in novel murine podocyte cell lines. Kidney Int. 66: 91–101. 15200416
- Schmidt, M.H., B. Chen, L.M. Randazzo, and O. Bogler. 2003. SETA/CIN85/Ruk and its binding partner AIP1 associate with diverse cytoskeletal elements, including FAKs, and modulate cell adhesion. J. Cell Sci. 116: 2845–2855. 12771190
- Schneider, T., C. Reiter, E. Eule, B. Bader, B. Lichte, Z. Nie, T. Schimansky, R.G. Ramos, and K.F. Fischbach. 1995. Restricted expression of the irreC-rst protein is required for normal axonal projections of columnar visual neurons. Neuron. 15: 259–271. 7646884
- Shih, N.Y., J. Li, V. Karpitskii, A. Nguyen, M.L. Dustin, O. Kanagawa, J.H. Miner, and A.S. Shaw. 1999. Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science. 286: 312–315. 10514378
- Shih, N.Y., J. Li, R. Cotran, P. Mundel, J.H. Miner, and A.S. Shaw. 2001. CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain. Am. J. Pathol. 159: 2303–2308. 11733379 PMC1850607
- Siripala, A.D., and M.D. Welch. 2007a. SnapShot: actin regulators I. Cell. 128: 626. 17289579
- Siripala, A.D., and M.D. Welch. 2007b. SnapShot: actin regulators II. Cell. 128: 1014. 17350583
- Take, H., S. Watanabe, K. Takeda, Z.X. Yu, N. Iwata, and S. Kajigaya. 2000. Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl. Biochem. Biophys. Res. Commun. 268: 321–328. 10679202
- Tepass, U., and K.P. Harris. 2007. Adherens junctions in Drosophila retinal morphogenesis. Trends Cell Biol. 17: 26–35. 17134901
- Veraksa, A., A. Bauer, and S. Artavanis-Tsakonas. 2005. Analyzing protein complexes in Drosophila with tandem affinity purification-mass spectrometry. Dev. Dyn. 232: 827–834. 15704125
- Welsch, T., N. Endlich, W. Kriz, and K. Endlich. 2001. CD2AP and p130Cas localize to different F-actin structures in podocytes. Am. J. Physiol. Renal Physiol. 281: F769–F777. 11553524
- Welsch, T., N. Endlich, G. Gokce, E. Doroshenko, J.C. Simpson, W. Kriz, A.S. Shaw, and K. Endlich. 2005. Association of CD2AP with dynamic actin on vesicles in podocytes. Am. J. Physiol. Renal Physiol. 289: F1134–F1143. 15956777
- Woroniecki, R.P., M. Schiffer, A.S. Shaw, F.J. Kaskel, and E.P. Bottinger. 2006. Glomerular expression of transforming growth factor-beta (TGF-beta) isoforms in mice lacking CD2-associated protein. Pediatr. Nephrol. 21: 333–338. 16388393
- Wu, C., Y.P. Wairkar, C.A. Collins, and A. DiAntonio. 2005. Highwire function at the Drosophila neuromuscular junction: spatial, structural, and temporal requirements. J. Neurosci. 25: 9557–9566. 16237161 PMC6725727
- Xu, T., and G.M. Rubin. 1993. Analysis of genetic mosaics in developing and adult Drosophila tissues. Development. 117: 1223–1237. 8404527
Cited by
Sorted by citations
Dourlen, P., Kilinc, D., Malmanche, N., Chapuis, J., & Lambert, J.-C. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02004-0 · Cited by 168 · see citing works
Shulman, J. M., Imboywa, S., Giagtzoglou, N., Powers, M. P., Hu, Y., Devenport, D., Chipendo, P., Chibnik, L. B., Diamond, A., Perrimon, N., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt478 · Cited by 167 · see citing works
The role of genetic risk factors of Alzheimer’s disease in synaptic dysfunction
Fu, W.-Y., & Ip, N. Y. (2023) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2022.07.011 · Cited by 48 · see citing works
Ojelade, S. A., Lee, T. V., Giagtzoglou, N., Yu, L., Ugur, B., Li, Y., Duraine, L., Zuo, Z., Petyuk, V., De Jager, P. L., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.041 · Cited by 42 · see citing works
- Authors
- Johnson, R. I., Seppa, M. J., & Cagan, R. L.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Washington University in St. Louis (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2008-03-24
- Volume
- 180
- Issue
- 6
- Pages
- 1191-1204
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2290846
- OpenAlex
- W2046239158
- Cited by
- 67
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 7 · 2012: 2
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Wesleyan University Digital Collections (Wesleyan University) (submittedVersion, public-domain)
- Funders
- National Institutes of Health
- National Eye Institute (R01-EY1149, R01EY011495)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Drosophila melanogaster, E-cadherin, cell adhesion, cell junctions, actin cytoskeleton, capping protein, cell motility, tissue patterning, retinal development, epithelial morphogenesis, cell death
- MeSH terms
- Actins, Animals, Cell Adhesion, Cytoskeletal Proteins, Cytoskeleton, Drosophila melanogaster, Embryo, Nonmammalian, Epithelium, Eye, Eye Proteins, Intercellular Junctions, Microfilament Proteins, Cell Adhesion Molecules, Neuronal, Cadherins, Gene Expression Regulation, Developmental, Body Patterning, Drosophila Proteins, Animals, Genetically Modified, Adaptor Proteins, Signal Transducing, Actin Capping Proteins
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