ORCID Profile
0000-0003-1412-3987
Current Organisation
University of North Carolina at Chapel Hill
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Publisher: The Company of Biologists
Date: 2019
DOI: 10.1242/DEV.180976
Abstract: Apical-basal polarity is a fundamental property of animal tissues. Drosophila embryos provide an outstanding model for defining mechanisms initiating and maintaining polarity. Polarity is initiated during cellularization, when cell-cell adherens junctions are positioned at the future boundary of apical and basolateral domains. Polarity maintenance then involves complementary and antagonistic interplay between apical and basal polarity complexes. The Scribble/Dlg module is well-known for promoting basolateral identity during polarity maintenance. Here we report a surprising role for Scribble/Dlg in polarity initiation, placing it near the top of the network positioning adherens junctions. Scribble and Dlg are enriched in nascent adherens junctions, are essential for adherens junction positioning and supermolecular assembly, and also play a role in basal junction assembly. We test hypotheses for the underlying mechanisms, exploring potential effects on protein trafficking, cytoskeletal polarity, or Par-1 localization/function. Our data suggest that the Scribble/Dlg module plays multiple roles in polarity initiation. Different domains of Scribble contribute to these distinct roles. Together these data reveal novel roles for Scribble/Dlg as master scaffolds regulating assembly of distinct junctional complexes at different times and places.
Publisher: American Society for Cell Biology (ASCB)
Date: 12-2002
Abstract: There are 10 known mammalian septin genes, some of which produce multiple splice variants. The current nomenclature for the genes and gene products is very confusing, with several different names having been given to the same gene product and distinct names given to splice variants of the same gene. Moreover, some names are based on those of yeast or Drosophilaseptins that are not the closest homologues. Therefore, we suggest that the mammalian septin field adopt a common nomenclature system, based on that adopted by the Mouse Genomic Nomenclature Committee and accepted by the Human Genome Organization Gene Nomenclature Committee. The human and mouse septin genes will be namedSEPT1–SEPT10 and Sept1–Sept10, respectively. Splice variants will be designated by an underscore followed by a lowercase “v” and a number, e.g., SEPT4_v1.
Publisher: Rockefeller University Press
Date: 31-12-2018
Abstract: Key events ranging from cell polarity to proliferation regulation to neuronal signaling rely on the assembly of multiprotein adhesion or signaling complexes at particular subcellular sites. Multidomain scaffolding proteins nucleate assembly and direct localization of these complexes, and the protein Scribble and its relatives in the LAP protein family provide a paradigm for this. Scribble was originally identified because of its role in apical–basal polarity and epithelial integrity in Drosophila melanogaster. It is now clear that Scribble acts to assemble and position erse multiprotein complexes in processes ranging from planar polarity to adhesion to oriented cell ision to synaptogenesis. Here, we explore what we have learned about the mechanisms of action of Scribble in the context of its multiple known interacting partners and discuss how this knowledge opens new questions about the full range of Scribble protein partners and their structural and signaling roles.
Publisher: Public Library of Science (PLoS)
Date: 11-04-2018
Publisher: The Company of Biologists
Date: 2017
DOI: 10.1242/DEV.157941
Abstract: Epithelial apical-basal polarity drives assembly and function of most animal tissues. Polarity initiation requires cell-cell adherens junction assembly at the apical-basolateral boundary. The mechanisms underlying polarity establishment remain key issues. Drosophila embryos provide a superb model, as 6000 polarized cells assemble simultaneously. Current data place the actin-junctional linker Canoe (Afadin's fly homolog) at the top of the polarity hierarchy, where it directs Bazooka/Par3 and adherens junctions positioning. Here we define mechanisms regulating Canoe localization/function. Spatial organization of Canoe is multifaceted, involving membrane-localization, recruitment to nascent junctions and macromolecular assembly at tricellular junctions. Our data suggest apical activation of the small GTPase Rap1 regulates all three events, but support multiple modes of regulation. The Rap1GEF Dizzy/PDZ-GEF is critical for Canoe tricellular junction enrichment but not apical retention. Canoe's Rap1-interacting RA-domains mediate adherens junction and tricellular junction recruitment but are dispensable for membrane-localization. Our data also support a role for Canoe-multimerization. These multifactorial inputs all shape Canoe localization, correct Bazooka/Par3 and adherens junction positioning, and thus apical-basal polarity. We integrate existing data into a new polarity establishment model.
Location: United States of America
No related grants have been discovered for Mark Peifer.