A5085801984- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
- Photosynthetic Processes and Mechanisms
- Ubiquitin and proteasome pathways
- Retinal Development and Disorders
- Pancreatic function and diabetes
- Calcium signaling and nucleotide metabolism
- Genomics and Chromatin Dynamics
- Erythrocyte Function and Pathophysiology
- Protist diversity and phylogeny
- Plant nutrient uptake and metabolism
- Photoreceptor and optogenetics research
- Cancer-related Molecular Pathways
- Receptor Mechanisms and Signaling
- Genetic and Kidney Cyst Diseases
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Amino Acid Enzymes and Metabolism
- RNA regulation and disease
- Genetics, Bioinformatics, and Biomedical Research
- Autophagy in Disease and Therapy
- Protein Kinase Regulation and GTPase Signaling
- Renal and related cancers
University of Oxford
2016-2025
Hôpital Nord
2021-2023
Centre Hospitalo-Universitaire Bab El Oued
2021
Science Oxford
2013
University of Liverpool
2007-2011
Max Planck Institute of Biochemistry
2000-2008
Max Planck Society
2001-2007
Guided Therapy Systems (United States)
2006
Vanderbilt University
2006
University of Glasgow
1999-2003
Oligodendrocytes secrete vesicles into the extracellular space, where they might play a role in neuron-glia communication. These exosomes are small with diameter of 50-100 nm that formed within multivesicular bodies and released after fusion plasma membrane. The intracellular pathways generate poorly defined. Because Rab family guanosine triphosphatases (GTPases) together their regulators important membrane trafficking organizers, we investigated which GTPase-activating proteins interfere...
Autophagy is a bulk degradation process characterized by the formation of double membrane vesicles called autophagosomes. The exact molecular mechanism autophagosome and origin autophagosomal remain unclear. We screened 38 human Tre-2/Bub2/Cdc16 domain–containing Rab guanosine triphosphatase–activating proteins (GAPs) identified 11 negative regulators starvation-induced autophagy. One these putative RabGAPs, TBC1D14, colocalizes interacts with autophagy kinase ULK1. Overexpressed TBC1D14...
Primary cilia are sensory structures involved in morphogen signalling during development, liquid flow the kidney, mechanosensation, sight, and smell (Badano, J.L., N. Mitsuma, P.L. Beales, Katsanis. 2006. Annu. Rev. Genomics Hum. Genet. 7:125–148; Singla, V., J.F. Reiter. Science. 313:629–633.). Mutations that affect primary responsible for several diseases, including neural tube defects, polycystic kidney disease, retinal degeneration, cancers (Badano et al., 2006; Singla Reiter, 2006)....
A key requirement for Rab function in membrane trafficking is site-specific activation by GDP-GTP exchange factors (GEFs), but the majority of 63 human Rabs have no known GEF. We performed a systematic characterization 17 DENN domain proteins and demonstrated that they are specific GEFs 10 Rabs. DENND1A/1B localize to clathrin patches at plasma activate Rab35 an endocytic pathway Shiga toxin trans-Golgi network. DENND2 target actin filaments control Rab9-dependent mannose-6-phosphate...
Hermansky-Pudlak syndrome (HPS) is a human disease characterized by partial loss of pigmentation and impaired blood clotting [1Di Pietro S.M. Dell'Angelica E.C. The cell biology syndrome: recent advances.Traffic. 2005; 6: 525-533Crossref PubMed Scopus (161) Google Scholar, 2Raposo G. Marks M.S. Melanosomes—dark organelles enlighten endosomal membrane transport.Nat. Rev. Mol. Cell Biol. 2007; 8: 786-797Crossref (386) 3Erickson R.P. Pigment, platelets, in mouse.Proc. Natl. Acad. Sci. USA....
PP2A-B55 is one of the major phosphatases regulating cell division. Despite its importance for temporal control during mitotic exit, how B55 substrates are recognized and differentially dephosphorylated unclear. Using phosphoproteomics combined with kinetic modeling to extract B55-dependent rate constants, we have systematically identified assigned their order in exit. These share a bipartite polybasic recognition determinant (BPR) flanking Cdk1 phosphorylation site. Experiments show that...
We have investigated the function of mitotic kinesin-like protein (MKlp) 2, a kinesin localized to central spindle, and demonstrate that its depletion results in failure cleavage furrow ingression cytokinesis, disrupts localization polo-like kinase 1 (Plk1). MKlp2 is target for Plk1, phosphorylated binds polo box domain Plk1. Plk1 also directly microtubules targets spindle via domain, this interaction controls activity toward MKlp2. An antibody neck region prevents phosphorylation by causes...
Mitotic kinases of the Polo and Aurora families are key regulators chromosome segregation cytokinesis. Here, we have investigated role MKlp1 MKlp2, two vertebrate mitotic kinesins essential for cytokinesis, in spatial regulation B kinase. Previously, demonstrated that MKlp2 recruits Polo-like kinase 1 (Plk1) to central spindle anaphase. We now find but not MKlp1-depleted cells B-INCENP complex remains at centromeres fails relocate spindle. exerts dual control over localization, because it is...
Multiple mitotic kinesins and microtubule-associated proteins (MAPs) act in concert to direct cytokinesis (Glotzer, M. 2005. Science. 307:1735–1739). In anaphase cells, many of these associate with an antiparallel array microtubules termed the central spindle. The MAP microtubule-bundling protein PRC1 (protein-regulating 1) is one key molecules required for integrity this structure (Jiang, W., G. Jimenez, N.J. Wells, T.J. Hope, G.M. Wahl, T. Hunter, R. Fukunaga. 1998. Mol. Cell. 2:877–885;...
The Golgi apparatus has long been suggested to be important for directing secretion specific sites on the plasma membrane in response extracellular signaling events. However, mechanisms by which events are coordinated with function remain poorly understood. Here, we identify a scaffolding matrix protein GM130 that sheds light how such may regulated. We show mammalian Ste20 kinases YSK1 and MST4 target via GM130. In addition, binding activates these promoting autophosphorylation of conserved...
Membrane traffic between the endoplasmic reticulum (ER) and Golgi apparatus through is a highly regulated process controlled by members of rab GTPase family. The GTP form rab1 regulates ER to transport interaction with vesicle tethering factor p115 cis-Golgi matrix protein GM130, also part complex GRASP65 important for organization cisternae. Here, we find that novel coiled-coil golgin-45 interacts medial-Golgi GRASP55 rab2 but not other proteins. Depletion disrupts causes block in secretory...
The mammalian Golgi complex is comprised of a ribbon stacked cisternal membranes often located in the pericentriolar region cell. Here, we report that during apoptosis fragmented into dispersed clusters tubulo-vesicular membranes. We have found fragmentation caspase dependent and identified GRASP65 (Golgi reassembly stacking protein 65 kD) as novel substrate. cleaved specifically by caspase-3 at conserved sites its membrane distal COOH terminus an early stage execution phase. Expression...
Rab GTPases control vesicle movement and tethering membrane events in trafficking. We used the 38 human GTPase activating proteins (GAPs) to identify which of 60 Rabs encoded genome function at Golgi complex. Surprisingly, this screen identified only two GAPs, RN-tre TBC1D20, disrupting both organization protein transport. is GAP for Rab43, controls retrograde transport into from endocytic pathway. TBC1D20 ER-localized Rab1, blocking delivery secretory cargo ER cell surface. Strikingly, its...
Polo-like kinase 1 (Plk1) is a key regulator of mitotic progression and cell division in eukaryotes. It highly expressed tumor cells considered potential target for cancer therapy. Here, we report the discovery application novel potent small-molecule inhibitor mammalian Plk1, ZK-Thiazolidinone (TAL). We have extensively characterized TAL vitro addressed specificity within by studying Plk1 functions sister chromatid separation, centrosome maturation, spindle assembly. Moreover, used detailed...