Protocadherin cis -dimer architecture and recognition unit diversity

Proceedings of the National Academy of Sciences of the United States of America
Kerry Marie GoodmanLawrence Shapiro

Abstract

Clustered protocadherins (Pcdhs) mediate numerous neural patterning functions, including neuronal self-recognition and non-self-discrimination to direct self-avoidance among vertebrate neurons. Individual neurons stochastically express a subset of Pcdh isoforms, which assemble to form a stochastic repertoire of cis-dimers. We describe the structure of a PcdhγB7 cis-homodimer, which includes the membrane-proximal extracellular cadherin domains EC5 and EC6. The structure is asymmetric with one molecule contributing interface surface from both EC5 and EC6, and the other only from EC6. Structural and sequence analyses suggest that all Pcdh isoforms will dimerize through this interface. Site-directed mutants at this interface interfere with both Pcdh cis-dimerization and cell surface transport. The structure explains the known restrictions of cis-interactions of some Pcdh isoforms, including α-Pcdhs, which cannot form homodimers. The asymmetry of the interface approximately doubles the size of the recognition repertoire, and restrictions on cis-interactions among Pcdh isoforms define the limits of the Pcdh recognition unit repertoire.

References

Jun 3, 2004·Genome Research·Gavin E CrooksSteven E Brenner
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Sep 7, 2004·The Journal of Biological Chemistry·Yoji MurataTakeshi Yagi
Dec 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Joshua A WeinerJoshua R Sanes
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jul 25, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shota KatoriTakeshi Yagi
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Dietmar Schreiner, Joshua A Weiner
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marion B RichardCharles A Greer
Oct 1, 2011·Nature Methods·Thomas Nordahl PetersenHenrik Nielsen
Oct 13, 2011·Molecular Systems Biology·Fabian SieversDesmond G Higgins
Jan 26, 2012·Frontiers in Molecular Neuroscience·Tuhina Prasad, Joshua A Weiner
Apr 21, 2012·Frontiers in Molecular Neuroscience·Takeshi Yagi
Jun 26, 2012·Journal of Molecular Cell Biology·Lun SuoQiang Wu
Sep 13, 2012·Frontiers in Molecular Neuroscience·Keizo HiranoTakeshi Yagi
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Jul 12, 2013·Annual Review of Neuroscience·S Lawrence Zipursky, Wesley B Grueber
Aug 1, 2013·Development·Weisheng V Chen, Tom Maniatis
Dec 10, 2013·Cell Reports·Kohei YoshitakeKatsuei Shibuki
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Dec 30, 2014·Chemical Senses·Kyutaro KawagishiTetsuji Moriizumi

❮ Previous
Next ❯

Citations

Oct 9, 2018·Annual Review of Cell and Developmental Biology·George MountoufarisTom Maniatis
Oct 15, 2019·The Journal of Comparative Neurology·Celia P MirallesAngel L De Blas
Nov 16, 2019·The FEBS Journal·G S SingarajuS Rakshit
Jan 30, 2019·Frontiers in Physiology·Ruth StyfhalsGraziano Fiorito
Sep 18, 2020·Neuroscience Bulletin·Qiang Wu, Zhilian Jia
Jul 23, 2020·Frontiers in Molecular Neuroscience·Anna PanchoEve Seuntjens
Sep 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Fengyan ZhouYongfeng Jin
Oct 10, 2018·Proceedings of the National Academy of Sciences of the United States of America·Andrew M GarrettRobert W Burgess
Mar 22, 2020·Nature Communications·Joseph S PakEngin Özkan
Jan 1, 2021·The Journal of Comparative Neurology·Nicole LaMassaGreg R Phillips
Dec 3, 2020·Frontiers in Neuroscience·Zhilian Jia, Qiang Wu
Mar 9, 2021·Acta Crystallographica. Section F, Structural Biology Communications·Michelle E Gray, Marcos Sotomayor
Dec 12, 2018·Biophysical Journal·Pedro De-la-TorreMarcos Sotomayor
Aug 28, 2021·International Journal of Molecular Sciences·Maxime LemieuxFrédéric Bretzner

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Basal Forebrain & Food Avoidance

Neurons in the basal forebrain play specific roles in regulating feeding. Here are the latest discoveries pertaining to the basal forebrain and food avoidance.