A5082309307- Cellular transport and secretion
- Hearing, Cochlea, Tinnitus, Genetics
- Lipid Membrane Structure and Behavior
- Protein Kinase Regulation and GTPase Signaling
- Endoplasmic Reticulum Stress and Disease
- Hearing Loss and Rehabilitation
- Mitochondrial Function and Pathology
- Photosynthetic Processes and Mechanisms
- Protease and Inhibitor Mechanisms
- 14-3-3 protein interactions
- Ubiquitin and proteasome pathways
- Vestibular and auditory disorders
- Peptidase Inhibition and Analysis
- Retinal Development and Disorders
- Blood properties and coagulation
- RNA and protein synthesis mechanisms
- Erythrocyte Function and Pathophysiology
- Molecular Sensors and Ion Detection
- Antimicrobial Peptides and Activities
- Enzyme Production and Characterization
- Photoreceptor and optogenetics research
- Electron Spin Resonance Studies
- Advanced MRI Techniques and Applications
- Advanced Chemical Physics Studies
- MRI in cancer diagnosis
University of Birmingham
2009-2020
Inserm
1986-2007
University of Edinburgh
2007
Université de Montpellier
1991-1998
Centre de Référence Déficits Immunitaires Héréditaires
1990
Hôpital Saint Charles
1983-1986
Collège de France
1986
Pujol R, Rebillard G, Puel J—L, Lenoir M, Eybalin Recasens M. Glutamate neurotoxicity in the cochlea: a possible consequence of ischaemic or anoxic occurring ageing. Acta Otolaryngol (Stockh) 1991; Suppl. 476:32—36.Glutamate is considered to be one most common neurotransmitters fast excitatory synapses central nervous system. On other hand, its excitotoxic properties are increasingly cited explain some brain damage linked with hypoxia and ischaemia: i.e., those that occur frequently An...
Four-phosphate-adaptor protein 1 (FAPP1) regulates secretory transport from the trans-Golgi network (TGN) to plasma membrane. FAPP1 is recruited Golgi through binding of its pleckstrin homology (PH) domain phosphatidylinositol 4-phosphate (PtdIns(4)P) and a small GTPase ADP-ribosylation factor (ARF1). Despite critical role in membrane trafficking, molecular basis dual function remains unclear. Here, we report 1.9 Å resolution crystal structure PH detail mechanisms PtdIns(4)P ARF1...
The mechanisms underlying Golgi targeting and vesiculation are unknown, although the responsible phosphatidylinositol 4‐phosphate (PtdIns(4)P) ligand four‐phosphate‐adaptor protein (FAPP) modules have been defined. micelle‐bound structure of FAPP1 pleckstrin homology domain reveals how its prominent wedge independently tubulates membranes by leaflet penetration. Mutations compromising exposed hydrophobicity full‐length FAPP2 abolish lipid monolayer binding compression. trafficking process...
Abstract Sorting nexins anchor trafficking machines to membranes by binding phospholipids. The paradigm of the superfamily is sorting nexin 3 (SNX3), which localizes early endosomes recognizing phosphatidylinositol 3-phosphate (PI3P) initiate retromer-mediated segregation cargoes trans-Golgi network (TGN). Here we report solution structure full length human SNX3, and show that PI3P recognition accompanied bilayer insertion a proximal loop in its extended Phox homology (PX) domain....
The function of a protein is determined by its intrinsic activity in the context subcellular distribution. Membranes localize proteins within cellular compartments and govern their specific activities. Discovering such membrane-protein interactions important for understanding biological mechanisms could uncover novel sites therapeutic intervention. We present method detecting membrane interactive exposed residues that insert into lipid bilayers. Although development process involved analysis...
The human genome encodes about 285 proteins that contain at least one annotated pleckstrin homology (PH) domain. As the first phosphoinositide binding module domain to be discovered, PH recruits diverse protein architectures cellular membranes. domains constitute of largest superfamilies, and have diverged regulate many different signaling modules such as Dbl (DH) Tec (TH) domains. ligands approximately 70 been validated by assays complexed structures, allowing meaningful extrapolation...
The Golgi-associated four-phosphate adaptor protein 2 (FAPP2) has been shown to possess transfer activity for glucosylceramide both in vitro and cells. We have previously that FAPP2 is involved apical transport from the Golgi complex epithelial MDCK In this paper we assign an unknown as well providing structural insight into assembly a low-resolution envelope structure. By applying analytical ultracentrifugation small-angle x-ray scattering, show dimeric solution, having curved shape 30 nm...
The comparative ototoxicity of four aminoglycosides (amikacin, dibekacin, gentamicin and tobramycin) was evaluated in the rat during critical period cochlear development. Newborn rats received a daily subcutaneous injection one antibiotics for 8 consecutive days, starting on day after birth (amikacin: 225 mg/kg, dibekacin: 60 tobramycin: 45 mg/kg). Evaluation assessed month end treatment using recordings (action potential microphonic), surface preparations scanning electron microscopy. No...
It was shown previously that an ankyrin-sensitive, phosphatidylethanolamine/phosphatidylcholine (PE/PC) binding site maps to the N-terminal part of ankyrin-binding domain β-spectrin (ankBDn). Here we have identified amino acid residues within this which are responsible for recognizing monolayers and bilayers composed PE/PC mixtures. In vitro studies revealed a quadruple mutant with substituted hydrophobic W1771, L1775, M1778 W1779 not only failed effectively bind PE/PC, but its residual...
Polymorphisms in the region of calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence diabetes, most common polymorphism resulting recognition by transcription factors and protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose processing human hepatocytes, there no known selective inhibitors CaMK1 kinases that can be used to validate or translate these findings. Here we describe development series potent,...
The outer hair cells (OHCs) from the mammalian organ of Corti are assumed to enhance sensitivity and selectivity cochlea via an electromotile response sound stimulation. These OHC mechanical changes feed energy back into before completion transduction process by inner cells. electromotility is thought depend on specific transmembrane motor proteins. Electron microscopy has been used previously image lateral plasma membrane, where voltage sensors motors located. A very regular organization...
Our group (Horner KC, Guieu R, Magnan J, Chays A, Cazals Y. Neuropsychopharmacology 26: 135-138, 2002) has earlier described hyperprolactinemia in some patients presenting inner ear dysfunction. However, that study, it was not possible to determine whether a cause or an effect of the symptoms. To investigate on function, we first developed model estrogen-primed Fischer 344 rats and then performed functional studies pigmented guinea pigs. Hyperprolactinemia induced, after 2 mo, hearing loss...
The small GTPase RhoA promotes deregulated signaling upon interaction with lymphoid blast crisis (Lbc), the oncogenic form of A-kinase anchoring protein 13 (AKAP13). onco-Lbc is a hyperactive Rho-specific guanine nucleotide exchange factor (GEF), but its structural mechanism has not been reported despite involvement in cardiac hypertrophy and cancer causation. pleckstrin homology (PH) domain Lbc located at C-terminal end shown here to specifically recognize activated rather than lipids....
Sorting nexin 3 (SNX3) belongs to a sub-family of sorting nexins that primarily contain single Phox homology domain capable binding phosphoinositides and membranes. We report the complete (1)H, (13)C (15)N resonance assignments full-length human SNX3 protein identification its secondary structure elements, revealing canonical fold unstructured termini.