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bettina winckler

Kelly Barford, Austin Keeler, Lloyd McMahon, Kathryn McDaniel, Chan Choo Yap, Christopher D Deppmann, Bettina Winckler
The development of the peripheral nervous system relies on long-distance signaling from target organs back to the soma. In sympathetic neurons, this long-distance signaling is mediated by target derived Nerve Growth Factor (NGF) interacting with its axonal receptor, TrkA. This ligand receptor complex internalizes into what is commonly referred to as the signaling endosome which is transported retrogradely to the soma and dendrites to mediate survival signaling and synapse formation, respectively. The molecular identity of signaling endosomes in dendrites has not yet been determined...
March 16, 2018: Scientific Reports
Huaye Zhang, Bettina Winckler, Qian Cai
No abstract text is available yet for this article.
March 2018: Developmental Neurobiology
Kelly Barford, Austin Keeler, Christopher Deppmann, Bettina Winckler
In neurons, correct targeting of receptors to the axon is critical for cell survival and circuit formation. In this issue of Developmental Cell, Yamashita et al. (2017) report that the ER-resident phosphatase PTP1B is required to prime TrkA for axonal transport.
September 25, 2017: Developmental Cell
James E Casanova, Bettina Winckler
Endosome maturation requires a coordinated change in the Rab GTPase and phosphoinositide composition of the endosomal membrane. In this issue, Liu et al. (2017. J. Cell Biol. identify WDR91 as a ubiquitous Rab7 effector that inhibits phosphatidylinositol 3-kinase activity on endosomes and is critical for endosome maturation, viability, and dendrite growth of neurons in vivo.
October 2, 2017: Journal of Cell Biology
Chan Choo Yap, Laura Digilio, Lloyd McMahon, Bettina Winckler
Membrane traffic critically regulates most aspects of neuronal function. Neurons express many neuronal-specific proteins that regulate membrane traffic, including the poorly understood small transmembrane proteins neural-specific gene 1 and 2 (Nsg1/NEEP21 and Nsg2/P19). Nsg1 has been implicated in regulating endosomal recycling and sorting of several important neuronal receptors. Nsg2 is largely unstudied. At steady-state, Nsg1 and Nsg2 only partially co-localize with known endosomal compartments, and it was suggested that they mark a neuronal-specific endosome...
September 5, 2017: Scientific Reports
Kelly Barford, Chan Choo Yap, Noelle D Dwyer, Bettina Winckler
Endosomal maturation and transport constitutes a complex trafficking system present in all cell types. Neurons have adapted their endosomal system to meet their unique and complex needs. These adaptations include repurposing existing proteins to diversify endocytosis and trafficking, as well as preferential expression of certain regulators more highly in neurons than other cell types. These neuronal regulators include the family of Neuron-Specific Gene family members (Nsg), NEEP21 (Nsg1), and P19 (Nsg2). NEEP21/Nsg1 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and β-APP...
June 1, 2017: Journal of Comparative Neurology
Chan Choo Yap, Laura Digilio, Lloyd McMahon, Matylda Roszkowska, Christopher J Bott, Kamil Kruczek, Bettina Winckler
Doublecortin on the X-chromosome (DCX) is a neuronal microtubule-binding protein with a multitude of roles in neurodevelopment. In humans, DCX is a major genetic locus for X-linked lissencephaly. The best studied defects are in neuronal migration during corticogenesis and in the hippocampus, as well as axon and dendrite growth defects. Much effort has been directed at understanding the molecular and cellular bases of DCX-linked lissencephaly. The focus has been in particular on defects in microtubule assembly and bundling, using knock-out mice and expression of WT and mutant Dcx in non-neuronal cells...
December 23, 2016: Journal of Biological Chemistry
Mikael Simons, Bettina Winckler
No abstract text is available yet for this article.
August 2016: Current Opinion in Neurobiology
Kelly Barford, Christopher Deppmann, Bettina Winckler
Neurons are the largest cells in the body and form subcellular compartments such as axons and dendrites. During both development and adulthood building blocks must be continually trafficked long distances to maintain the different regions of the neuron. Beyond building blocks, signaling complexes are also transported, allowing for example, axons to communicate with the soma. The critical roles of signaling via ligand-receptor complexes is perhaps best illustrated in the context of development, where they are known to regulate polarization, survival, axon outgrowth, dendrite development, and synapse formation...
April 2017: Developmental Neurobiology
Zofia M Lasiecka, Bettina Winckler
Endosomes play critical roles on regulating surface receptor levels as well as signaling cascades in all cell types, including neurons. Endocytosis and endosomal trafficking is routinely studied after fixation, but live imaging is increasingly being used to capture the dynamic nature of endosomes and is allowing increasingly sophisticated glimpses into trafficking processes in live neurons. In this chapter, we describe the basics of neuronal primary cultures, methods for expressing fluorescent proteins, and live imaging of cargos and endosomal regulators...
2016: Methods in Cell Biology
Laura Digilio, Chan Choo Yap, Bettina Winckler
The brain consists of many distinct neuronal cell types, but which cell types are present in widely used primary cultures of embryonic rodent brain is often not known. We characterized how abundantly four cell type markers (Ctip2, Satb2, Prox1, GAD65) were represented in cultured rat neurons, how easily neurons expressing different markers can be transfected with commonly used plasmids, and whether neuronal-enriched endosomal proteins Nsg-1 (NEEP21) and Nsg-2 (P19) are ubiquitously expressed in all types of cultured neurons...
2015: PloS One
Chan Choo Yap, Bettina Winckler
Proper cortical development depends on the orchestrated actions of a multitude of guidance receptors and adhesion molecules and their downstream signaling. The levels of these receptors on the surface and their precise locations can greatly affect guidance outcomes. Trafficking of receptors to a particular surface locale and removal by endocytosis thus feed crucially into the final guidance outcomes. In addition, endocytosis of receptors can affect downstream signaling (both quantitatively and qualitatively) and regulated endocytosis of guidance receptors is thus an important component of ensuring proper neural development...
2015: Frontiers in Cellular Neuroscience
Zofia M Lasiecka, Chan Choo Yap, Joshua Katz, Bettina Winckler
The function of endosomes is intricately linked to cellular function in all cell types, including neurons. Intriguingly, neurons express cell type-specific proteins that localize to endosomes, but little is known about how these neuronal proteins interface with canonical endosomes and ubiquitously expressed endosomal components, such as EEA1 (Early Endosomal Antigen 1). NEEP21 (Neuronal Early Endosomal Protein 21 kDa) localizes to somatodendritic endosomes, and downregulation of NEEP21 perturbs the correct trafficking of multiple receptors, including glutamate receptors (GluA2) during LTP and amyloidogenic processing of βAPP...
October 29, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Deblina Dey, Veit-Simon Eckle, Iuliia Vitko, Kyle A Sullivan, Zofia M Lasiecka, Bettina Winckler, Ruth L Stornetta, John M Williamson, Jaideep Kapur, Edward Perez-Reyes
OBJECTIVE: To develop a constitutively active K(+) leak channel using TREK-1 (TWIK-related potassium channel 1; TREK-M) that is resistant to compensatory down-regulation by second messenger cascades, and to validate the ability of TREK-M to silence hyperactive neurons using cultured hippocampal neurons. To test if adenoassociated viral (AAV) delivery of TREK-M could reduce the duration of status epilepticus and reduce neuronal death induced by lithium-pilocarpine administration. METHODS: Molecular cloning techniques were used to engineer novel vectors to deliver TREK-M via plasmids, lentivirus, and AAV using a cytomegalovirus (CMV)-enhanced GABRA4 promoter...
February 2014: Epilepsia
Veit-Simon Eckle, Aleksandr Shcheglovitov, Iuliia Vitko, Deblina Dey, Chan Choo Yap, Bettina Winckler, Edward Perez-Reyes
T-type calcium channels play essential roles in regulating neuronal excitability and network oscillations in the brain. Mutations in the gene encoding Cav3.2 T-type Ca(2+) channels, CACNA1H, have been found in association with various forms of idiopathic generalized epilepsy. We and others have found that these mutations may influence neuronal excitability either by altering the biophysical properties of the channels or by increasing their surface expression. The goals of the present study were to investigate the excitability of neurons expressing Cav3...
February 15, 2014: Journal of Physiology
Chan Choo Yap, Bettina Winckler
The sodium-proton exchanger NHE6 contributes to proper endosomal acidification. NHE6 mutations are also linked to autism-related disorders. In this issue of Neuron, using NHE6-knockout mice, Ouyang et al. (2013) uncover how dysregulation of endosomal pH leads to disturbances in BDNF signaling and neuronal morphogenesis defects.
October 2, 2013: Neuron
Xiaoqin Fu, Kristy J Brown, Chan Choo Yap, Bettina Winckler, Jyoti K Jaiswal, Judy S Liu
Doublecortin (Dcx) is the causative gene for X-linked lissencephaly, which encodes a microtubule-binding protein. Axon tracts are abnormal in both affected individuals and in animal models. To determine the reason for the axon tract defect, we performed a semiquantitative proteomic analysis of the corpus callosum in mice mutant for Dcx. In axons from mice mutant for Dcx, widespread differences are found in actin-associated proteins as compared with wild-type axons. Decreases in actin-binding proteins α-actinin-1 and α-actinin-4 and actin-related protein 2/3 complex subunit 3 (Arp3), are correlated with dysregulation in the distribution of filamentous actin (F-actin) in the mutant neurons with increased F-actin around the cell body and decreased F-actin in the neurites and growth cones...
January 9, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Chan Choo Yap, Max Vakulenko, Kamil Kruczek, Bashir Motamedi, Laura Digilio, Judy S Liu, Bettina Winckler
Doublecortin on X chromosome (DCX) is one of two major genetic loci underlying human lissencephaly, a neurodevelopmental disorder with defects in neuronal migration and axon outgrowth. DCX is a microtubule-binding protein, and much work has focused on its microtubule-associated functions. DCX has other reported binding partners, including the cell adhesion molecule neurofascin, but the functional significance of the DCX-neurofascin interaction is not understood. Neurofascin localizes strongly to the axon initial segment in mature neurons, where it plays a role in assembling and maintaining other axon initial segment components...
May 30, 2012: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Chan Choo Yap, Bettina Winckler
Endocytosis and endosomal trafficking play a multitude of roles in cellular function beyond regulating entry of essential nutrients. In this review, we discuss the cell biological principles of endosomal trafficking, the neuronal adaptations to endosomal organization, and the role of endosomal trafficking in neural development. In particular, we consider how cell fate decisions, polarity, migration, and axon outgrowth and guidance are influenced by five endosomal tricks: dynamic modulation of receptor levels by endocytosis and recycling, cargo-specific responses via cargo-specific endocytic regulators, cell-type-specific endocytic regulation, ligand-specific endocytic regulation, and endosomal regulation of ligand processing and trafficking...
May 10, 2012: Neuron
Zofia M Lasiecka, Bettina Winckler
Neurons are polarized cells that have a complex and unique morphology: long processes (axons and dendrites) extending far from the cell body. In addition, the somatodendritic and axonal domains are further divided into specific subdomains, such as synapses (pre- and postsynaptic specializations), proximal and distal dendrites, axon initial segments, nodes of Ranvier, and axon growth cones. The striking asymmetry and complexity of neuronal cells are necessary for their function in receiving, processing and transferring electrical signals, with each domain playing a precise function in these processes...
December 2011: Molecular and Cellular Neurosciences
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