5k6w Citations

Molecular basis of sidekick-mediated cell-cell adhesion and specificity.

Abstract

Sidekick (Sdk) 1 and 2 are related immunoglobulin superfamily cell adhesion proteins required for appropriate synaptic connections between specific subtypes of retinal neurons. Sdks mediate cell-cell adhesion with homophilic specificity that underlies their neuronal targeting function. Here we report crystal structures of Sdk1 and Sdk2 ectodomain regions, revealing similar homodimers mediated by the four N-terminal immunoglobulin domains (Ig1-4), arranged in a horseshoe conformation. These Ig1-4 horseshoes interact in a novel back-to-back orientation in both homodimers through Ig1:Ig2, Ig1:Ig1 and Ig3:Ig4 interactions. Structure-guided mutagenesis results show that this canonical dimer is required for both Sdk-mediated cell aggregation (via trans interactions) and Sdk clustering in isolated cells (via cis interactions). Sdk1/Sdk2 recognition specificity is encoded across Ig1-4, with Ig1-2 conferring the majority of binding affinity and differential specificity. We suggest that competition between cis and trans interactions provides a novel mechanism to sharpen the specificity of cell-cell interactions.

Reviews - 5k6w mentioned but not cited (1)

  1. Structure and Functions of Sidekicks. Yamagata M. Front Mol Neurosci 13 139 (2020)

Articles - 5k6w mentioned but not cited (3)

  1. Molecular basis of sidekick-mediated cell-cell adhesion and specificity. Goodman KM, Yamagata M, Jin X, Mannepalli S, Katsamba PS, Ahlsén G, Sergeeva AP, Honig B, Honig B, Sanes JR, Shapiro L. Elife 5 e19058 (2016)
  2. Architecture of cell-cell adhesion mediated by sidekicks. Tang H, Chang H, Dong Y, Guo L, Shi X, Wu Y, Huang Y, He Y. Proc Natl Acad Sci U S A 115 9246-9251 (2018)
  3. Mechanisms underlying distinct subcellular localization and regulation of epithelial long myosin light-chain kinase splice variants. Chanez-Paredes SD, Abtahi S, Zha J, Li E, Marsischky G, Zuo L, Grey MJ, He W, Turner JR. J Biol Chem 300 105643 (2024)


Reviews citing this publication (4)

Articles citing this publication (14)

  1. Retinal Ganglion Cell Diversity and Subtype Specification from Human Pluripotent Stem Cells. Langer KB, Ohlemacher SK, Phillips MJ, Fligor CM, Jiang P, Gamm DM, Meyer JS. Stem Cell Reports 10 1282-1293 (2018)
  2. Sidekick Is a Key Component of Tricellular Adherens Junctions that Acts to Resolve Cell Rearrangements. Letizia A, He D, Astigarraga S, Colombelli J, Hatini V, Llimargas M, Treisman JE. Dev Cell 50 313-326.e5 (2019)
  3. Cadherins Interact With Synaptic Organizers to Promote Synaptic Differentiation. Yamagata M, Duan X, Sanes JR. Front Mol Neurosci 11 142 (2018)
  4. The tricellular vertex-specific adhesion molecule Sidekick facilitates polarised cell intercalation during Drosophila axis extension. Finegan TM, Hervieux N, Nestor-Bergmann A, Fletcher AG, Blanchard GB, Sanson B. PLoS Biol 17 e3000522 (2019)
  5. DIP/Dpr interactions and the evolutionary design of specificity in protein families. Sergeeva AP, Katsamba PS, Cosmanescu F, Brewer JJ, Ahlsen G, Mannepalli S, Shapiro L, Honig B. Nat Commun 11 2125 (2020)
  6. Expression and Roles of the Immunoglobulin Superfamily Recognition Molecule Sidekick1 in Mouse Retina. Yamagata M, Sanes JR. Front Mol Neurosci 11 485 (2018)
  7. Drosophila Sidekick is required in developing photoreceptors to enable visual motion detection. Astigarraga S, Douthit J, Tarnogorska D, Creamer MS, Mano O, Clark DA, Meinertzhagen IA, Treisman JE. Development 145 dev158246 (2018)
  8. How clustered protocadherin binding specificity is tuned for neuronal self-/nonself-recognition. Goodman KM, Katsamba PS, Rubinstein R, Ahlsén G, Bahna F, Mannepalli S, Dan H, Sampogna RV, Shapiro L, Honig B, Honig B. Elife 11 e72416 (2022)
  9. Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry. Ray NR, Kunkle BW, Hamilton-Nelson K, Kurup JT, Rajabli F, Qiao M, Vardarajan BN, Cosacak MI, Kizil C, Jean-Francois M, Cuccaro M, Reyes-Dumeyer D, Cantwell L, Kuzma A, Vance JM, Gao S, Hendrie HC, Baiyewu O, Ogunniyi A, Akinyemi RO, Alzheimer's Disease Genetics Consortium, Lee WP, Martin ER, Wang LS, Beecham GW, Bush WS, Xu W, Jin F, Wang L, Farrer LA, Haines JL, Byrd GS, Schellenberg GD, Mayeux R, Pericak-Vance MA, Reitz C. Alzheimers Dement 20 5247-5261 (2024)
  10. Loss of a newly discovered microRNA in Chinese hamster ovary cells leads to upregulation of N-glycolylneuraminic acid sialylation on monoclonal antibodies. Fischer S, Mathias S, Stadermann A, Yang S, Schmieder V, Zeh N, Schmidt N, Richter P, Wright S, Zimmermann E, Ley Y, van der Meer J, Hartsch T, Bernloehr C, Otte K, Bradl H, Gamer M, Schulz P. Biotechnol Bioeng 119 832-844 (2022)
  11. Expression and Roles of Lynx1, a Modulator of Cholinergic Transmission, in Skeletal Muscles and Neuromuscular Junctions in Mice. Doss SV, Barbat-Artigas S, Lopes M, Pradhan BS, Prószyński TJ, Robitaille R, Valdez G. Front Cell Dev Biol 10 838612 (2022)
  12. New binding specificities evolve via point mutation in an invertebrate allorecognition gene. Huene AL, Chen T, Nicotra ML. iScience 24 102811 (2021)
  13. A web-based survey on various symptoms of computer vision syndrome and the genetic understanding based on a multi-trait genome-wide association study. Yoshimura K, Morita Y, Konomi K, Ishida S, Fujiwara D, Kobayashi K, Tanaka M. Sci Rep 11 9446 (2021)
  14. Molecular mechanism of contactin 2 homophilic interaction. Fan S, Liu J, Chofflet N, Bailey AO, Russell WK, Zhang Z, Takahashi H, Ren G, Rudenko G. Structure 32 1652-1666.e8 (2024)