Lipidated morphogens can spread within tissues to regulate cell fate during development or tissue repair. How these insoluble molecules reach distant target cells remains unclear. Reporting in Nature, McGough et al. (2020) reveal the secret of how the cell-surface proteoglycan Dally-like-protein (Dlp) promotes long-range signaling of the palmitoylated morphogen Wingless.
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http://dx.doi.org/10.1016/j.devcel.2020.08.011 | DOI Listing |
Cells
July 2024
Shanxi Key Laboratory of Nucleic Acid Biopesticides, Research Institute of Applied Biology, Shanxi University, Taiyuan 030006, China.
Glypicans are closely associated with organ development and tumorigenesis in animals. Dally-like (Dlp), a membrane-bound glypican, plays pivotal roles in various biological processes in . In this study, we observed that an excess of Dlp led to the malformation of legs, particularly affecting the distal part.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Cell Biology, Emory University School of Medicine.
Rapidly dividing cells can eliminate slow growing neighbors through the apoptotic process of cell competition. This process ensures that only high fitness cells populate embryonic tissues and is proposed to underlie the ability of oncogene-transformed cells to progressively replace normal cells within a tissue. Patches of cells in the wing disc overexpressing the oncogenic Taiman (Tai) transcriptional coactivator kill normal neighbors by secreting Spz ligands that trigger pro-apoptotic Toll signaling in receiving cells.
View Article and Find Full Text PDFCells
February 2024
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Nicolás Cabrera 1, E-28049 Madrid, Spain.
Glypicans (Glps) are a family of heparan sulphate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glps are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), among others. In the Hh-signalling pathway, Glps have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix, and for unimpaired ligand reception in distant recipient cells.
View Article and Find Full Text PDFElife
January 2024
Growth & Development, Biozentrum, Spitalstrasse, University of Basel, Basel, Switzerland.
Dpp/BMP acts as a morphogen to provide positional information in the wing disc. Key cell-surface molecules to control Dpp morphogen gradient formation and signaling are heparan sulfate proteoglycans (HSPGs). In the wing disc, two HSPGs, the glypicans Division abnormally delayed (Dally) and Dally-like (Dlp) have been suggested to act redundantly to control these processes through direct interaction of their heparan sulfate (HS) chains with Dpp.
View Article and Find Full Text PDFJ Biol Chem
January 2024
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address:
Heparan sulfate proteoglycans (HSPGs) are composed of a core protein and glycosaminoglycan (GAG) chains and serve as coreceptors for many growth factors and morphogens. To understand the molecular mechanisms by which HSPGs regulate morphogen gradient formation and signaling, it is important to determine the relative contributions of the carbohydrate and protein moieties to the proteoglycan function. To address this question, we generated ΔGAG alleles for dally and dally-like protein (dlp), two Drosophila HSPGs of the glypican family, in which all GAG-attachment serine residues are substituted to alanine residues using CRISPR/Cas9 mutagenesis.
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