A5057339032- Cellular transport and secretion
- Pancreatic function and diabetes
- Retinal Development and Disorders
- Lipid Membrane Structure and Behavior
- Ion Transport and Channel Regulation
- Drug Transport and Resistance Mechanisms
- Microtubule and mitosis dynamics
- Cystic Fibrosis Research Advances
- Lysosomal Storage Disorders Research
- Erythrocyte Function and Pathophysiology
- Calcium signaling and nucleotide metabolism
- Glycosylation and Glycoproteins Research
- Advanced biosensing and bioanalysis techniques
- Autoimmune and Inflammatory Disorders Research
- Ion channel regulation and function
- Signaling Pathways in Disease
- Immune Cell Function and Interaction
- Neonatal Respiratory Health Research
- Electrolyte and hormonal disorders
- Cytomegalovirus and herpesvirus research
- Magnesium in Health and Disease
- melanin and skin pigmentation
- Peptidase Inhibition and Analysis
- Protein Interaction Studies and Fluorescence Analysis
- Biomedical Research and Pathophysiology
Utrecht University
2011-2024
University Medical Center Utrecht
2009-2021
Heidelberg University
2008-2021
University Hospital Heidelberg
2008-2021
University of Groningen
1985-2018
Duke Medical Center
2010
Radboud University Nijmegen
2009
Institute of Cell Biology
2002
University Medical Center
2001
Yale University
1991-1996
The retromer complex mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network (TGN). Mammalian is composed a sorting nexin (SNX) dimer that binds phosphatidylinositol 3-phosphate–enriched endosomal membranes and vacuolar protein (Vps) 26/29/35 trimer participates in recognition. mammalian SNX necessary but not sufficient for recruitment Vps26/29/35 membranes. In this study, we demonstrate guanosine triphosphatase Rab7 contributes recruitment....
During receptor mediated endocytosis, at least a fraction of recycling cargo typically accumulates in pericentriolar cluster tubules and vesicles. However, it is not clear if these endosomal structures are biochemically distinct from the early endosomes which they derived. To better characterize this endosome population, we determined distribution two endogenous proteins known to be functionally involved [Rab4, cellubrevin (Cbvn)] relative ligand [transferrin (Tfn)] as traversed endocytic...
Small GTP-binding proteins of the rab family have been implicated as playing important roles in controlling membrane traffic on biosynthetic and endocytic pathways. We demonstrate that a distinct protein, rab4p, is associated with population early endosomes involved transferrin-receptor recycling. An antibody to human rab4p was found detect doublet approximately 24-kDa immunoblots from various cell types. Seventy-five percent these were tightly bound could be released only by detergent...
Mutations in the aquaporin-2 (AQP2) water channel gene cause autosomal recessive nephrogenic diabetes insipidus (NDI). Here we report first patient with an dominant form of NDI, which is caused by a G866A transition AQP2 one allele, resulting E258K substitution C-tail AQP2. To define molecular NDI this patient, AQP2-E258K was studied Xenopus oocytes. In contrast to wild-type AQP2, conferred small increase permeability, reduced expression at plasma membrane. Coexpression AQP2-E258K, but not...
In renal collecting ducts, a vasopressin-induced cAMP increase results in the phosphorylation of aquaporin-2 (AQP2) water channels at Ser-256 and its redistribution from intracellular vesicles to apical membrane. Hormones that activate protein kinase C (PKC) proteins counteract this process. To determine role putative sites trafficking hormonal regulation human AQP2, three casein II (Ser-148, Ser-229, Thr-244), one PKC (Ser-231), A (Ser-256) site were altered mimic constitutively...
To regulate mammalian water homeostasis, arginine-vasopressin (AVP) induces phosphorylation and thereby redistribution of renal aquaporin-2 (AQP2) channels from vesicles to the apical membrane. Vice versa, AVP (or forskolin) removal hormones activating PKC cause AQP2 internalization, but mechanism is unknown. Here, we show that a fraction modified with two three ubiquitin moieties in vitro vivo. Mutagenesis revealed ubiquitinated one K63-linked chain at K270 only. In Madin-Darby canine...
Griscelli syndrome type 2 (GS2) is a genetic disorder in which patients exhibit life-threatening defects of cytotoxic T lymphocytes (CTLs) whose lytic granules fail to dock on the plasma membrane and therefore do not release their contents. The disease caused by absence functional rab27a, but how rab27a controls secretion granule contents remains elusive. Mutations Munc13-4 cause familial hemophagocytic lymphohistiocytosis subtype 3 (FHL3), phenotypically related GS2. We show that direct...
Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by a broad phenotypic spectrum that includes seizures, mental retardation, renal dysfunction and dermatological abnormalities. Mutations to either the <i>TSC1</i> or<i>TSC2</i> gene are responsible for disease. The<i>TSC1</i> encodes hamartin, 130-kDa protein without significant homology other known mammalian proteins. Analysis of amino acid sequence tuberin, 200-kDa product the<i>TSC2</i> gene, identified region with...
UDP-galactose:ceramide galactosyltransferase (CGalT) transfers UDP-galactose to ceramide form the glycosphingolipid galactosylceramide. Galactosylceramide is major constituent of myelin and also highly enriched in many epithelial cells, where it thought play an important role lipid protein sorting. Although biochemical pathways biosynthesis are relatively well understood, localization enzymes involved these processes has remained controversial. We here have raised antibodies against CGalT...
Most peroxisomal matrix proteins contain a carboxyl-terminal tripeptide that directs them to peroxisomes. Within limits, these amino acids may be varied, without loss of function. The specificity this targeting signal (PTS1) is remarkable considering its small size and relaxed consensus sequence. Moreover, several have PTS1-like does not fit the reported Because many PTS1 variants seem functional in species-dependent or protein context-dependent manner, we investigated requirements...
Protein kinase B (PKB)/Akt is known to promote cell migration, and this may contribute the enhanced invasiveness of malignant cells. To elucidate potential mechanisms by which PKB/Akt promotes migration phenotype, we have investigated its role in endosomal transport recycling integrins. Whereas internalization alpha v beta 3 5 1 integrins their compartment were independent PKB/Akt, return these (but not internalized transferrin) plasma membrane was regulated phosphatidylinositol 3-kinases...
Aquaporin-2 (AQP2) is a pore-forming protein that required for regulated reabsorption of water from urine. Mutations in AQP2 lead to nephrogenic diabetes insipidus, disorder which functional not expressed on the apical cell surface kidney collecting duct principal cells. The mechanisms and pathways directing endoplasmic reticulum Golgi complex beyond have been defined. We found ∼25% newly synthesized glycosylated. Nonglycosylated complex-glycosylated wild-type are stable proteins with...
Phosphatidylinositol 4-kinasebeta (PI4Kbeta) plays an essential role in maintaining the structural integrity of Golgi complex. In a search for PI4Kbeta-interacting proteins, we found that PI4Kbeta specifically interacts with GTP-bound form small GTPase rab11. The PI4Kbeta-rab11 interaction is functional significance because inhibition rab11 binding to abolished localization complex and significantly inhibited transport vesicular stomatitis virus G protein from plasma membrane. We propose...
A;lthough glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of in membrane transport, we used glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that cells do not make melanin pigment because tyrosinase, first rate-limiting enzyme synthesis, was targeted to melanosomes but accumulated Golgi complex. However, tyrosinase-related protein 1 still reached...
The endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function plasticity. However, the molecular mechanisms that organize specific endocytic routes are poorly understood. Here, we identify GRIP-associated protein-1 (GRASP-1) as a neuron-specific effector of Rab4 key component machinery coordinates recycling endosome maturation dendrites. We show GRASP-1 necessary AMPA recycling, maintenance spine morphology, At level, segregates from...