- Erythrocyte Function and Pathophysiology
- Pancreatic function and diabetes
- Cellular transport and secretion
- Ion channel regulation and function
- Blood properties and coagulation
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Neurogenesis and neuroplasticity mechanisms
- Hemoglobin structure and function
- Cellular Mechanics and Interactions
- Cardiac electrophysiology and arrhythmias
- Axon Guidance and Neuronal Signaling
- Neonatal Health and Biochemistry
- Protein Structure and Dynamics
- Hemoglobinopathies and Related Disorders
- Force Microscopy Techniques and Applications
- Microtubule and mitosis dynamics
- Glycosylation and Glycoproteins Research
- Photoreceptor and optogenetics research
- Diabetes and associated disorders
- RNA and protein synthesis mechanisms
- Caveolin-1 and cellular processes
- Connexins and lens biology
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
Duke University Hospital
2011-2025
Duke Medical Center
2013-2025
Duke University
2011-2021
Howard Hughes Medical Institute
2009-2018
Centre for Cancer Biology
2014
The Ohio State University Wexner Medical Center
2014
The Ohio State University
2014
Institute of Cell Biology
2008-2014
Institute of Neurobiology
2010
American Heart Association
2005
KCNQ (K V 7) potassium channels underlie subthreshold M-currents that stabilize the neuronal resting potential and prevent repetitive firing of action potentials. Here, antibodies against four different KCNQ2 KCNQ3 polypeptide epitopes show these subunits concentrated at axonal initial segment (AIS) node Ranvier. AIS concentration KCNQ3, like voltage-gated sodium (Na ) channels, is abolished in ankyrin-G knock-out mice. A short motif, common to mediates both vivo interaction retention AIS....
Voltage-gated sodium channels (NaCh) are colocalized with isoforms of the membrane-skeletal protein ankyrinG at axon initial segments, nodes Ranvier, and postsynaptic folds mammalian neuromuscular junction. The role in directing NaCh localization to segments was evaluated by region-specific knockout mouse cerebellum. Mutant mice exhibited a progressive ataxia beginning around postnatal day P16 subsequent loss Purkinje neurons. In mutant cerebella, were absent from granule cell neurons, cells...
We have characterized a new ankyrin gene, expressed in brain and other tissues, that is subject to extensive tissue-specific alternative mRNA processing. The full-length polypeptide has molecular mass of 480 kDa includes predicted globular head domain, with membrane- spectrin-binding activities, as well an extended "tail" domain. term this gene ankyrinG based on its giant size general expression. Two brain-specific isoforms 270 were identified contain unique stretch sequence highly enriched...
The axon initial segment is an excitable membrane highly enriched in voltage-gated sodium channels that integrates neuronal inputs and initiates action potentials. This study identifies Nav1.6 as the channel isoform at mature Purkinje neuron segments reports essential role for ankyrin-G coordinating physiological assembly of Nav1.6, βIV spectrin, L1 cell adhesion molecules (L1 CAMs) neurofascin NrCAM cerebellar neurons. Ankyrin-G spectrin appear by postnatal day 2, whereas CAMs are not fully...
A 43,000-dalton proteolytic fragment of the cytoplasmic domain band 3 was purified, and monospecific antibodies against this were prepared.1z61-Labeled associated with pure ankyrin in solution, a KO 8 X lo"' M stoichiometry 0.85 mol fragment/mol (with limiting concentrations ankyrin).Anti-43,000dalton IgG, which cross-reacted only 3, immunoprecipitated ankyrin, 4.2, as well from detergent extracts membranes, provided these not denatured.1261-Labeled selectively surface inside-out vesicles...
Pages 1029–1065: Vann Bennett. “Spectrin-Based Membrane Skeleton: A Multipotential Adaptor Between Plasma and Cytoplasm.” Page 1056: Ref. 36 should read BENNETT, H., J. CONDEELIS. Isolation of an immunoreactive analogue brain fodrin that is associated with the cell cortex Dictyostelium amoebae. Cell Motil. Cytoskeleton 11: 303–317, 1988.
We identify a human mutation (E1053K) in the ankyrin-binding motif of Na v 1.5 that is associated with Brugada syndrome, fatal cardiac arrhythmia caused by altered function 1.5. The E1053K abolishes binding to ankyrin-G, and also prevents accumulation at cell surface sites ventricular cardiomyocytes. Ankyrin-G are both localized intercalated disc T-tubule membranes cardiomyocytes, coimmunoprecipitates 190-kDa ankyrin-G from detergent-soluble lysates rat heart. These data suggest associates...
A specific association between spectrin and the inner surface of human erythrocyte membrane has been examined by measuring binding purified [32P]spectrin to inside out, spectrin-depleted vesicles right side out ghost vesicles. Spectrin was labeled incubating erythrocytes with 32Pi, eluted from membranes extraction in 0.3 mM NaPO4, pH 7.6. [32P]Spectrin separated actin other proteins isolated a nonaggregated state as So20,w = 7 S (in NaPO4) or 8 20 KCl, protein after sedimentation on linear...
Actin, spectrin, and associated molecules form a periodic sub-membrane lattice structure in axons. How this membrane skeleton is developed why it preferentially forms axons are unknown. Here, we studied the developmental mechanism of structure. We found that emerged early during axon development propagated from proximal regions to distal ends Components initial segment were recruited late development. Formation was regulated by local concentration βII which higher than dendrites. Increasing...
Neurofascin, NrCAM, L1, and NgCAM are a family of Ig/FNIII cell adhesion molecules that share ankyrin-binding activity in their cytoplasmic domains, candidates to form membrane-spanning complexes with members the ankyrin spectrin-binding proteins variety cellular contexts nervous system. Specialized forms ankyrin, 270 kD and/or 480 ankyrinG components membrane undercoat axons at node Ranvier. This paper focuses on definition isoforms localized nodal axon segment. The exon usage two major...
220-kDa ankyrin-B is required for coordinated assembly of Na/Ca exchanger, Na/K ATPase, and inositol trisphosphate (Ins P 3 ) receptor at transverse-tubule/sarcoplasmic reticulum sites in cardiomyocytes. A loss-of-function mutation identified an extended kindred causes a dominantly inherited cardiac arrhythmia, initially described as type 4 long QT syndrome. Here we report the identification eight unrelated probands harboring mutations, including four previously undescribed whose clinical...
Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that believed to play important roles in development of the nervous system. This report presents biochemical evidence these associate directly ankyrins, a family spectrin-binding proteins located on surface specialized plasma membrane domains. Rat neurofascin NrCAM together comprise over 0.5% protein adult brain tissue. Linkage ankyrin-binding spectrin-based...