title: The Alg5 ortholog Wollknäuel is essential for correct epidermal differentiation during Drosophila late embryogenesis.
abstract: The formation of an extracellular matrix (ECM) presupposes an ordered delivery of its components to ensure its stereotypic architecture. The Drosophila cuticle is an ECM produced by the epidermis at its apical site and is characterized by a layered organization. To understand the mechanisms of cuticle assembly during development, we have investigated early aspects of protein N-glycosylation, i.e. the attachment of a dolichol-linked oligosaccharide to distinct Asn sites of a protein known to be essential for sorting in the secretory pathway. Mutations in the Drosophila alg5 gene wollknäuel (wol) that codes for an enzyme initiating the glucosylation of the dolichol-linked oligosaccharide decrease, as expected, glucosylation and the amounts of N-glycosylated proteins such as the cuticle-organizing factor Knickkopf, without affecting their correct localization. At the same time, the polarity determinants Crumbs and atypical protein kinase C accumulate at the apical plasma membrane in wol deficient embryos. In part, these perturbations may also be caused by the unfolded protein response, which is commonly triggered by ER stress and downsizes transcription and translation in general. In any case, they are associated with the loss of cuticle layering and aberrant apical plasma membrane organization suggesting that glucosylation, either directly or indirectly through controlling protein degradation, is important for the efficient and balanced deployment of the biochemical functions of secreted and membrane-associated proteins during epidermal differentiation.
authors.affiliation: Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
authors.forename: Khaleelulla Saheb
authors.initials: KS
authors.lastname: Shaik
authors.forename: Martin
authors.initials: M
authors.lastname: Pabst
authors.forename: Heinz
authors.initials: H
authors.lastname: Schwarz
authors.forename: Friedrich
authors.initials: F
authors.lastname: Altmann
authors.forename: Bernard
authors.initials: B
authors.lastname: Moussian
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics* / Q000378:metabolism; D006031:Glycosylation; D017510:Protein Folding
chemical_list: D029721:Drosophila Proteins; D005964:Glucosyltransferases; C530856:WOL protein, Drosophila