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Publications

Nandadasa Lab Pub Med Listings

Total: 14 results
  • A new mouse mutant with cleavage-resistant versican and isoform-specific versican mutants demonstrate that proteolysis at the Glu441-Ala442 peptide bond in the V1 isoform is essential for interdigital web regression

    Jul 01 2021
    Author(s): Sumeda Nandadasa,Cyril Burin des Roziers,Christopher Koch,Karin Tran-Lundmark,María T Dours-Zimmermann,Dieter R Zimmermann,Sophie Valleix,Suneel S Apte
    Source: Matrix biology plus
    Two inherent challenges in the mechanistic interpretation of protease-deficient phenotypes are defining the specific substrate cleavages whose reduction generates the phenotypes and determining whether the phenotypes result from loss of substrate function, substrate accumulation, or loss of a function(s) embodied in the substrate fragments. Hence, recapitulation of a protease-deficient phenotype by a cleavage-resistant substrate would stringently validate the importance of a proteolytic event...
  • The versican-hyaluronan complex provides an essential extracellular matrix niche for Flk1+ hematoendothelial progenitors

    Jan 17 2021
    Author(s): Sumeda Nandadasa,Anna O'Donnell,Ayako Murao,Yu Yamaguchi,Ronald J Midura,Lorin Olson,Suneel S Apte
    Source: Matrix biology : journal of the International Society for Matrix Biology
    Little is known about extracellular matrix (ECM) contributions to formation of the earliest cell lineages in the embryo. Here, we show that the proteoglycan versican and glycosaminoglycan hyaluronan are associated with emerging Flk1^(+) hematoendothelial progenitors at gastrulation. The mouse versican mutant Vcan^(hdf) lacks yolk sac vasculature, with attenuated yolk sac hematopoiesis. CRISPR/Cas9-mediated Vcan inactivation in mouse embryonic stem cells reduced vascular endothelial and...
  • Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth

    Sep 10 2020
    Author(s): Sumeda Nandadasa,Jason M Szafron,Vai Pathak,Sae-Il Murtada,Caroline M Kraft,Anna O'Donnell,Christian Norvik,Clare Hughes,Bruce Caterson,Miriam S Domowicz,Nancy B Schwartz,Karin Tran-Lundmark,Martina Veigl,David Sedwick,Elliot H Philipson,Jay D Humphrey,Suneel S Apte
    Source: eLife
    The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At...
  • A disintegrin-like and metalloproteinase domain with thrombospondin type 1 motif 9 (ADAMTS9) regulates fibronectin fibrillogenesis and turnover

    May 16 2019
    Author(s): Lauren W Wang,Sumeda Nandadasa,Douglas S Annis,Joanne Dubail,Deane F Mosher,Belinda B Willard,Suneel S Apte
    Source: The Journal of biological chemistry
    The secreted metalloprotease ADAMTS9 has dual roles in extracellular matrix (ECM) turnover and biogenesis of the primary cilium during mouse embryogenesis. Its gene locus is associated with several human traits and disorders, but ADAMTS9 has few known interacting partners or confirmed substrates. Here, using a yeast two-hybrid screen for proteins interacting with its C-terminal Gon1 domain, we identified three putative ADAMTS9-binding regions in the ECM glycoprotein fibronectin. Using...
  • Secreted metalloproteases ADAMTS9 and ADAMTS20 have a non-canonical role in ciliary vesicle growth during ciliogenesis

    Mar 01 2019
    Author(s): Sumeda Nandadasa,Caroline M Kraft,Lauren W Wang,Anna O'Donnell,Rushabh Patel,Heon Yung Gee,Kay Grobe,Timothy C Cox,Friedhelm Hildebrandt,Suneel S Apte
    Source: Nature communications
    Although hundreds of cytosolic or transmembrane molecules form the primary cilium, few secreted molecules are known to contribute to ciliogenesis. Here, homologous secreted metalloproteases ADAMTS9 and ADAMTS20 are identified as ciliogenesis regulators that act intracellularly. Secreted and furin-processed ADAMTS9 bound heparan sulfate and was internalized by LRP1, LRP2 and clathrin-mediated endocytosis to be gathered in Rab11 vesicles with a unique periciliary localization defined by...
  • Mutations of ADAMTS9 Cause Nephronophthisis-Related Ciliopathy

    Jan 05 2019
    Author(s): Yo Jun Choi,Jan Halbritter,Daniela A Braun,Markus Schueler,David Schapiro,John Hoon Rim,Sumeda Nandadasa,Won-Il Choi,Eugen Widmeier,Shirlee Shril,Friederike Körber,Sidharth K Sethi,Richard P Lifton,Bodo B Beck,Suneel S Apte,Heon Yung Gee,Friedhelm Hildebrandt
    Source: American journal of human genetics
    Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are associated with defects in primary cilium structure and function. To identify genes mutated in NPHP-RC, we performed homozygosity mapping and whole-exome sequencing for >100 individuals, some of whom were single affected individuals born to consanguineous parents and some of whom were siblings of indexes who were also affected by NPHP-RC. We then performed high-throughput exon sequencing in a worldwide...
  • Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis

    Dec 10 2017
    Author(s): Keiichi Asano,Courtney M Nelson,Sumeda Nandadasa,Noriko Aramaki-Hattori,Daniel J Lindner,Tyler Alban,Junko Inagaki,Takashi Ohtsuki,Toshitaka Oohashi,Suneel S Apte,Satoshi Hirohata
    Source: Scientific reports
    The proteoglycan versican is implicated in growth and metastases of several cancers. Here we investigated a potential contribution of stromal versican to tumor growth and angiogenesis. We initially determined versican expression by several cancer cell lines. Among these, MDA-MB231 and B16F10 had none to minimal expression in contrast to Lewis lung carcinoma (LLC). Notably, tumors arising from these cell lines had higher versican levels than the cell lines themselves suggesting a contribution...
  • Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion

    Jun 15 2016
    Author(s): Brian A Benz,Sumeda Nandadasa,Megumi Takeuchi,Richard C Grady,Hideyuki Takeuchi,Rachel K LoPilato,Shinako Kakuda,Robert P T Somerville,Suneel S Apte,Robert S Haltiwanger,Bernadette C Holdener
    Source: Developmental biology
    Protein O-fucosyltransferase 2 (POFUT2) adds O-linked fucose to Thrombospondin Type 1 Repeats (TSR) in 49 potential target proteins. Nearly half the POFUT2 targets belong to the A Disintegrin and Metalloprotease with ThromboSpondin type-1 motifs (ADAMTS) or ADAMTS-like family of proteins. Both the mouse Pofut2 RST434 gene trap allele and the Adamts9 knockout were reported to result in early embryonic lethality, suggesting that defects in Pofut2 mutant embryos could result from loss of...
  • ADAMTS9-Mediated Extracellular Matrix Dynamics Regulates Umbilical Cord Vascular Smooth Muscle Differentiation and Rotation

    Jun 02 2015
    Author(s): Sumeda Nandadasa,Courtney M Nelson,Suneel S Apte
    Source: Cell reports
    Despite the significance for fetal nourishment in mammals, mechanisms of umbilical cord vascular growth remain poorly understood. Here, the secreted metalloprotease ADAMTS9 is shown to be necessary for murine umbilical cord vascular development. Restricting it to the cell surface using a gene trap allele, Adamts9(Gt), impaired umbilical vessel elongation and radial growth via reduced versican proteolysis and accumulation of extracellular matrix (ECM). Both Adamts9(Gt) and conditional Adamts9...
  • The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis

    Jan 22 2014
    Author(s): Sumeda Nandadasa,Simon Foulcer,Suneel S Apte
    Source: Matrix biology : journal of the International Society for Matrix Biology
    Embryonic development is an exceptionally dynamic process, requiring a provisional extracellular matrix that is amenable to rapid remodeling, and proteolytic or non-proteolytic mechanisms that can remodel the major components of this matrix. Versican is a chondroitin-sulfate proteoglycan that forms highly hydrated complexes with hyaluronan and is widely distributed in the provisional matrix of mammalian embryos. It has been extensively studied in the context of cardiovascular morphogenesis,...
  • Regulation of classical cadherin membrane expression and F-actin assembly by alpha-catenins, during Xenopus embryogenesis

    Jun 22 2012
    Author(s): Sumeda Nandadasa,Qinghua Tao,Amanda Shoemaker,Sang-Wook Cha,Christopher Wylie
    Source: PloS one
    Alpha (α)-E-catenin is a component of the cadherin complex, and has long been thought to provide a link between cell surface cadherins and the actin skeleton. More recently, it has also been implicated in mechano-sensing, and in the control of tissue size. Here we use the early Xenopus embryos to explore functional differences between two α-catenin family members, α-E- and α-N-catenin, and their interactions with the different classical cadherins that appear as tissues of the embryo become...
  • Nectin-2 and N-cadherin interact through extracellular domains and induce apical accumulation of F-actin in apical constriction of Xenopus neural tube morphogenesis

    Mar 25 2010
    Author(s): Hitoshi Morita,Sumeda Nandadasa,Takamasa S Yamamoto,Chie Terasaka-Iioka,Christopher Wylie,Naoto Ueno
    Source: Development (Cambridge, England)
    Neural tube formation is one of the most dynamic morphogenetic processes of vertebrate development. However, the molecules regulating its initiation are mostly unknown. Here, we demonstrated that nectin-2, an immunoglobulin-like cell adhesion molecule, is involved in the neurulation of Xenopus embryos in cooperation with N-cadherin. First, we found that, at the beginning of neurulation, nectin-2 was strongly expressed in the superficial cells of neuroepithelium. The knockdown of nectin-2...
  • N- and E-cadherins in Xenopus are specifically required in the neural and non-neural ectoderm, respectively, for F-actin assembly and morphogenetic movements

    Mar 13 2009
    Author(s): Sumeda Nandadasa,Qinghua Tao,Nikhil R Menon,Janet Heasman,Christopher Wylie
    Source: Development (Cambridge, England)
    Transmembrane cadherins are calcium-dependent intercellular adhesion molecules. Recently, they have also been shown to be sites of actin assembly during adhesive contact formation. However, the roles of actin assembly on transmembrane cadherins during development are not fully understood. We show here, using the developing ectoderm of the Xenopus embryo as a model, that F-actin assembly is a primary function of both N-cadherin in the neural ectoderm and E-cadherin in the non-neural (epidermal)...
  • G-protein-coupled signals control cortical actin assembly by controlling cadherin expression in the early Xenopus embryo

    Jun 15 2007
    Author(s): Qinghua Tao,Sumeda Nandadasa,Pierre D McCrea,Janet Heasman,Christopher Wylie
    Source: Development (Cambridge, England)
    During embryonic development, each cell of a multicellular organ rudiment polymerizes its cytoskeletal elements in an amount and pattern that gives the whole cellular population its characteristic shape and mechanical properties. How does each cell know how to do this? We have used the Xenopus blastula as a model system to study this problem. Previous work has shown that the cortical actin network is required to maintain shape and rigidity of the whole embryo, and its assembly is coordinated...