Project Details
Projekt
FOR 721: Molecular Structure and Function of the Tight Junction
Subject Area
Medicine
Biology
Biology
Term
from 2006 to 2012
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 21131654
Tight Junctions (occluding junctions, Zonulae occludentes) consist of proteins which interconnect laterally neighbouring cells of epithelia and endothelia. Some kinds of these proteins seal the tight junction, so that a nearly impermeable barrier develops, others even form channels, which allow for permeation between the cells. Accordingly, epithelia of different tightness are formed: "Tight" epithelia like large intestine, distal nephron, epidermis, and brain capillaries or "leaky" epithelia like small intestine, proximal nephron, and peritoneum.
The tight junction proteins occludin, tricellulin and the 24 members of the claudin family are characterised by four transmembrane domains and two extracellular loops. These loops contact like the teeth of a zipper with appropriate loops from the neighbouring cell membrane. Tight junctions are regulated in its molecular composition and ultrastructure, and function by intracellular adapter proteins and by the cytoskeleton. This regulation serves physiologic adaptation but also occurs in several epithelial/endothelial diseases.
The groups involved are from the Charité Berlin, as well as from the Leibniz Institute for Molecular Pharmacology (FMP) and the Max Delbrück Center for Molecular Medicine (MDC), both in Berlin-Buch. Main topics are the functions of distinct tight junction proteins as barrier or channel formers for solutes and water, characteristics of the tight junction in inflammatory bowel diseases, posttranslational modifications of tight junction proteins, the relation between renal tight junction proteins and blood pressure control, and the molecular structure of claudin-claudin interactions.
Aim of this project is to clarify the relationship between molecular structure and function of tight junction proteins, as well as their regulation and their role in diseases. The results may form a basis for future diagnostical and therapeutical approaches to diseases which seem not to have much in common but are characterised by defects of organ barriers, like Crohn's disease, renal hypertension, inner ear deafness, and cancerous diseases.
The tight junction proteins occludin, tricellulin and the 24 members of the claudin family are characterised by four transmembrane domains and two extracellular loops. These loops contact like the teeth of a zipper with appropriate loops from the neighbouring cell membrane. Tight junctions are regulated in its molecular composition and ultrastructure, and function by intracellular adapter proteins and by the cytoskeleton. This regulation serves physiologic adaptation but also occurs in several epithelial/endothelial diseases.
The groups involved are from the Charité Berlin, as well as from the Leibniz Institute for Molecular Pharmacology (FMP) and the Max Delbrück Center for Molecular Medicine (MDC), both in Berlin-Buch. Main topics are the functions of distinct tight junction proteins as barrier or channel formers for solutes and water, characteristics of the tight junction in inflammatory bowel diseases, posttranslational modifications of tight junction proteins, the relation between renal tight junction proteins and blood pressure control, and the molecular structure of claudin-claudin interactions.
Aim of this project is to clarify the relationship between molecular structure and function of tight junction proteins, as well as their regulation and their role in diseases. The results may form a basis for future diagnostical and therapeutical approaches to diseases which seem not to have much in common but are characterised by defects of organ barriers, like Crohn's disease, renal hypertension, inner ear deafness, and cancerous diseases.
DFG Programme
Research Units
Projects
- Alterationen von Occludin bei oxidativem Stress und Aufklärung der Funktion von Claudin-12 (Applicant Blasig, Ingolf )
- Barrierefunktion von Tight Junctions in Keratinocyten, Hautäquivalenten und in der Haut (Applicant Brandner, Johanna Maria )
- Charakterisierung von Tight Junction-Proteinen als Barriere- oder Kanalbildner (Applicant Fromm, Michael )
- Gefrierbruch-Elektronenmikroskopie der Tight Junction und allgemeine Aufgaben (Applicant Fromm, Michael )
- Molekulare und strukturelle Muster parazellulärer Poren durch subtypabhängige Claudin-Claudin-Wechselwirkungen in Tight Junctions (Applicant Krause, Gerd )
- Posttranslationale Modulation der Tight Junction-Struktur und -Funktion (Applicants Huber, Otmar ; Tauber, Rudolf )
- Renale Claudine und ihre Interaktionen (Applicant Günzel, Dorothee )
- Tight Junction-Proteine als Regulatoren der Permeabilität des Perineuriums und der Antinozizeption perineural applizierter Pharmaka (Applicants Fromm, Michael ; Rittner, Heike Lydia )
- Tight Junction-Proteine bei entzündlichen Darmerkrankungen (Applicant Schulzke, Jörg-Dieter )
- Tight Junction-Proteine: Rolle in der Ionenhomöostase und Blutdruckregulation (Applicant Müller, Dominik )
Spokesperson
Professor Dr. Michael Fromm
