Jan M Gebauer

University of Cologne | UOC · Institute of Biochemistry

In plants, host-pathogen coevolution often manifests in reciprocal, adaptive genetic changes through variations in host nucleotide-binding leucine-rich repeat immune receptors (NLRs) and virulence-promoting pathogen effectors. In grass powdery mildew (PM) fungi, an extreme expansion of a RNase-like effector family, termed RALPH, dominates the effec...

In plants, host-pathogen coevolution often manifests in reciprocal, adaptive genetic changes through variations in host nucleotide-binding leucine-rich repeat immune receptors (NLR) and virulence-promoting pathogen effectors. In grass powdery mildew (PM) fungi, an extreme expansion of a RNase-like effector family, termed RALPH, dominates the effect...

Bone morphogenetic proteins (BMP) are powerful regulators of cellular processes such as proliferation, differentiation, and apoptosis. However, the specific molecular requirements controlling the bioavailability of BMPs in the extracellular matrix (ECM) are not yet fully understood. Our previous work showed that BMPs are targeted to the ECM as grow...

Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/Interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded NADases produce signaling...

Plant pathogen-activated immune signaling by nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal Toll/Interleukin-1 receptor (TIR) domain converges on Enhanced Disease Susceptibility 1 (EDS1) and its direct partners Phytoalexin Deficient 4 (PAD4) or Senescence-Associated Gene 101 (SAG101). TIR-encoded NADases produce signaling...

Collagens play important roles in development and homeostasis in most higher organisms. In order to function, collagens require the specific chaperone HSP47 for proper folding and secretion. HSP47 is known to bind to the collagen triple-helix but the exact positions and numbers of binding sites are not clear. Here, we employed a collagen II peptide...

Heat shock protein 47 (HSP47), encoded by the SERPINH1 gene, is a molecular chaperone essential for correct folding of collagens. We report a homozygous p.(R222S) substitution in HSP47 in a child with severe osteogenesis imperfecta leading to early demise. p.R222 is a highly conserved residue located within the collagen interacting surface of HSP47...

The extracellular matrix (ECM) is the architect of multicellular organisms. The use of various model organisms has helped decipher the mechanisms by which the ECM provides both chemical and mechanical cues that regulate fundamental cellular processes conserved during evolution such as cell migration, invasion, and differentiation. High-throughput,...

Although collagens are the most abundant proteins implicated in various disease pathways, essential mechanisms required for their proper folding and assembly are poorly understood. Heat‐shock protein 47 (HSP47), an ER‐resident chaperone, was mainly reported to fulfill key functions in folding and secretion of fibrillar collagens by stabilizing pro‐...

Collagen VI is a ubiquitous heterotrimeric protein of the extracellular matrix (ECM) that plays an essential role in the proper maintenance of skeletal muscle. Mutations in collagen VI lead to a spectrum of congenital myopathies, from the mild Bethlem Myopathy to the severe Ullrich Congenital Muscular Dystrophy. Collagen VI contains only a short tr...

Type VII collagen is an extracellular matrix protein which is important for skin stability; however, detailed information at the molecular level is scarce. The second vWFA (von‐Willebrand‐factor type A) domain of type VII collagen mediates important interactions, and immunization of mice induces skin blistering in certain strains. To understand vWF...

Kollagenmodellpeptide sind vielversprechende Materialien für biomedizinische Anwendungen. Einblicke in die Auswirkungen von Strukturmodifikationen sind für die rationale Entwicklung von Peptideigenschaften entscheidend. Der Einfluss einer kovalenten Diprolin‐Versteifung wurde untersucht und mit theoretischen Ergebnissen korreliert, um die Zusammenw...

Collagen model peptides (CMPs) serve as tools for understanding stability and function of the collagen triple helix and have a potential for biomedical applications. In the past, interstrand cross‐linking or conformational preconditioning of proline units through stereoelectronic effects have been utilized in the design of stabilized CMPs. To furth...

Proteins are the building blocks of life. While proteins and their localization within cells and sub-cellular compartments are well defined, the proteins predicted to be secreted to form the extracellular matrix - or matrisome - remain elusive in the model organism C. elegans. Here, we used a bioinformatic approach combining gene orthology and prot...

Abstract COMP (cartilage oligomeric matrix protein) is a member of the thrombospondin family and forms homopentamers as well as mixed heterooligomers with its closely related family member TSP-4. COMP is long known to bind to collagens and to influence collagen fibril formation. Recent work indicates that already intracellular interaction with coll...

Pigment epithelium-derived factor (PEDF) is a multifunctional extracellular protein. In addition to its known antiangiogenic and neurotrophic roles in collagen rich tissues, PEDF is thought to be involved in collagen fibril assembly due to its sequence specific binding to the collagen fibril and high expression in regions of active bone formation....

Heat shock protein 47 is an ER (endoplasmic reticulum) resident collagen-specific chaperone and essential for proper formation of the characteristic collagen triple helix. It preferentially binds to the folded conformation of its clients and accompanies them from the ER to the Golgi compartment where it releases them and is recycled back to the ER....

Collagen XXVIII is the last discovered member of the collagen superfamily and thus has been only sparsely investigated. We studied collagen XXVIII in zebrafish to gain insight into its structure, evolution and expression. In contrast to human and mouse, the zebrafish genome contains four collagen XXVIII genes, col28a1a and -b, and col28a2a and -b....

Hsp47 is an essential collagen specific chaperone that is crucial for proper formation of the collagen triple helix. KO-mice die at an early emybronic state and missense mutations are linked to severe forms of osteogenesis imperfecta (Ishida & Nagata, 2011). On the other hand, Hsp47 is strongly upregulated in fibrotic pathogenies and has in proof-o...

Fraser syndrome (FS) is a phenotypically variable, autosomal recessive disorder characterized by cryptophthalmus, cutaneous syndactyly and other malformations resulting from mutations in FRAS1, FREM2 and GRIP1. Transient embryonic epidermal blistering causes the characteristic defects of the disorder. Fras1, Frem1 and Frem2 form the extracellular F...

Collagen is the most abundant protein in animals and is a major component of the extracellular matrix in tissues such as skin and bone. A distinctive structural feature of all collagen types is a unique triple-helical structure formed by tandem repeats of the consensus sequence Xaa-Yaa-Gly, in which Xaa and Yaa frequently are proline and hydroxypro...

Zebrafish fin mutants can be classed in two phenotypic groups. (A–X) Lateral Normarski images of the mutants pinfin (B–C, J–K, R–S), blasenta90 (D, L, T), rafelsfr23 (E,M,U), nageltq207 (F, N, V), fransentc17 (G, O, W) and badfinfr21 (H, P, X) displaying medial fin defects compared to wild-type embryos (A,I,Q). Embryos are shown at 32 hpf (A–H), 48...

Pectoral and adult tail fin phenotypes. (A–I) Lateral views of pectoral fins at 72 hpf showing the blisters (red arrows) present in pifte262/te262 (B), piftm95/ttm95 (C), blata90/ta90 (D), neltq207/tq207 (E), stutd204/td204 (F) and rflfr23/fr23 (G) embryos compared to WT (A). The dysmorphogenesis of the pectoral pins in fratc17/tc17 (H) and bdffr21...

Synergistic interaction and compound mutant/morphant analyses. (A–T) Demonstration of synergistic interactions between itga3 and lama5 (A–D), fras1 and frem2a (E–H), hmcn1 and fbn2 (I–L), and fras1 and hmcn1 (M–P), but not hmcn1 and lama5 (Q–T). Images show lateral views of embryos tails at 30 hpf (I–L), 36 hpf (E–H) or 48 hpf (A–D; M–T) after inje...

Confirmation of morphant phenotypes with second morpholino. Injection of second non-overlapping morpholinos was used to verify morphant phenotypes. Injection of translation-blocking morpholinos against fras1 (A), frem1a (B) and frem2b (D) into WT embryos realised blisters in the fin fold comparable to those seen with the original morpholinos. The f...

Fras1 distribution is compromised in sturgeon mutant fins. Transverse sections of WT (A) or stu−/− (B) posterior medial fins at 32 hpf, fluorescently immunostained for Fras1 (green), p63 (pink) and DAPI (blue). The extent of relative proximal extension of Fras1 protein appears reduced in stu−/− embryos (B) compared to WT (A). Extent of Fras1 staini...

Nature of molecular lesions in nel alleles. (A–B) Sequence chromatograms of hmcn1 cDNA from neltq207/tq207 (A) and nelfr22/fr22 (B) are shown with mutant sequence given below the WT sequence above. Whilst the neltq207 allele displays a nonsense mutation, the nelfr22 allele showed double peaks from nucleotide 8538 onwards, suggestive of aberrant spl...

Using forward genetics, we have identified the genes mutated in two classes of zebrafish fin mutants. The mutants of the first class are characterized by defects in embryonic fin morphogenesis, which are due to mutations in a Laminin subunit or an Integrin alpha receptor, respectively. The mutants of the second class display characteristic blisteri...

AMACO is a basement membrane associated protein that belongs to the VWA domain-containing protein superfamily. In addition to three VWA domains it contains two EGF-like domains, a cysteine-rich domain and a unique domain. Mouse AMACO has been partially characterized, but its function remains unknown. The zebrafish genome contains a single AMACO ort...

The VWA domain-containing extracellular matrix protein AMACO has not been extensively characterized and its function remains unknown. It has been proposed as a potential cancer marker and carries a rare O-glucosylation and O-fucosylation on its first EGF-like domain. AMACO is a basement membrane associated protein, however its exact localization ha...

AMACO (VWA2 protein) is an extracellular matrix protein of unknown function associated with certain basement membranes in skin, lung, and kidney. AMACO is a member of the von Willebrand factor A-like (VWA) domain containing protein superfamily and in addition to three VWA domains it also contains two epidermal growth factor-like domains. One of the...

The matrilins form a family of non-collagenous adaptor proteins in the extracellular matrix. The extracellular ligand interactions of matrilins have been studied in some detail, while the potential interplay between matrilins and cells has been largely neglected. Except for matrilin-4, all matrilins mediate cell attachment, but only for matrilin-1...