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BACKGROUND To establish and maintain their polarized morphology, neurons employ active transport driven by molecular motors to sort cargo between axons and dendrites. However, the basic traffic rules governing polarized transport on neuronal microtubule arrays are unclear. RESULTS Here we show that the microtubule minus-end-directed motor dynein is(More)
In neurons, the distinct molecular composition of axons and dendrites is established through polarized targeting mechanisms, but it is currently unclear how nonpolarized cargoes, such as mitochondria, become uniformly distributed over these specialized neuronal compartments. Here, we show that TRAK family adaptor proteins, TRAK1 and TRAK2, which link(More)
The formation of complex nervous systems requires processes that coordinate proliferation, migration and differentiation of neuronal cells. The remarkable morphological transformations of neurons as they migrate, extend axons and dendrites and establish synaptic connections, imply a strictly regulated process of structural organization and dynamic(More)
BACKGROUND Protein aggregation and the formation of intracellular inclusions are a central feature of many neurodegenerative disorders, but precise knowledge about their pathogenic role is lacking in most instances. Here we have characterized inclusions formed in transgenic mice carrying the P56S mutant form of VAPB that causes various motor neuron(More)
The vesicle-associated membrane protein (VAMP) associated protein B (VAPB) is an integral membrane protein localized to the endoplasmic reticulum (ER). The P56S mutation in VAPB has been linked to motor neuron degeneration in amyotrophic lateral sclerosis type 8 (ALS8) and forms ER-like inclusions in various model systems. However, the role of wild-type and(More)
Tubulin tyrosine ligase (TTL) catalyzes the post-translational retyrosination of detyrosinated α-tubulin. Despite the indispensable role of TTL in cell and organism development, its molecular mechanism of action is poorly understood. By solving crystal structures of TTL in complex with tubulin, we here demonstrate that TTL binds to the α and β subunits of(More)
Development, polarization, structural integrity, and plasticity of neuronal cells critically depend on the microtubule network and its dynamic properties. SLAIN1 and SLAIN2 are microtubule plus-end tracking proteins that have been recently identified as regulators of microtubule dynamics. SLAINs are targeted to microtubule tips through an interaction with(More)
OBJECTIVE Periventricular leukomalacia (PVL) is part of a spectrum of cerebral white matter injury which is associated with adverse neurodevelopmental outcome in preterm infants. While PVL is common in neonates with cardiac disease, both before and after surgery, it is less common in older infants with cardiac disease. Pre-, intra-, and postoperative risk(More)
OBJECTIVE The objective of Part II is to analyze the dataset of extracted hemodynamic features (Case 3 of Part I) through computational intelligence (CI) techniques for identification of potential prognostic factors for periventricular leukomalacia (PVL) occurrence in neonates with congenital heart disease. METHODS The extracted features (Case 3 dataset(More)
Neurons are highly specialized for the processing and transmission of electrical signals and use cytoskeleton-based motor proteins to transport different vesicles and cellular materials. Abnormalities in intracellular transport are thought to be a critical factor in the degeneration and death of neurons in both the central and peripheral nervous systems.(More)