We provide the first characterization of a novel signaling adapter, Nesca, in neurotrophic signal transduction. Nesca contains a RUN domain, a WW domain, a leucine zipper, a carboxyl-terminal SH3 domain, and several proline-rich regions. Nesca is highly expressed in the brain, is serine phosphorylated, and mobilizes from the cytoplasm to the nuclear membrane in response to neurotrophin, but not...

Members of the neurotrophin gene family and their high-affinity Trk receptors control innervation of the cochlea during embryonic development. Lack of neurotrophin signalling in the cochlea has been well documented for early postnatal animals, resulting in a loss of cochlear sensory neurones and a region-specific reduction of target innervation along the tonotopic axis. However, how reduced neu...

Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurall...

Neurite outgrowth is one of the essential processes underlying development and plasticity of the nervous system. Enhancing neurite outgrowth, along with neural protection, is one of the most prominent therapeutic strategies against neuronal degeneration or damage. The sigma-1 receptor (Sig-1R) is a brain-enriched a receptor chaperone expressed in the ER membrane. As Sig-1R is involved in the mo...

Kidins220/ARMS is a transmembrane protein playing a crucial role in neuronal and cardiovascular development. Kidins220/ARMS is a downstream target of neurotrophin receptors and interacts with several signalling and trafficking factors. Through computational modelling, we found two potential sites for alternative splicing of Kidins220/ARMS. The first is located between exon 24 and exon 29, while...

Basal forebrain GABAergic and cholinergic circuits regulate the activity of cholinergic projections to the cortex and hippocampus. Because these projections influence cortical development and function, the development of basal forebrain excitatory and inhibitory neurons is critical for overall brain development. We show that the neurotransmitter phenotype of these neurons is developmentally reg...

Nerve growth factor (NGF) and neurotrophin-3 (NT-3) mediate activities such as survival, differentiation, and proliferation in various subsets of neurons. In this report, we define precisely the residues in human NGF responsible for NGF biological activity and binding specificity to the neurotrophin receptor TrkA. In earlier studies we defined five amino acid residues of NGF which confer NGF-li...

Lipid rafts, cholesterol and lipid rich microdomains, are believed to play important roles as platforms for the partitioning of transmembrane and synaptic proteins involved in synaptic signaling, plasticity, and maintenance. There is increasing evidence of a physical interaction between post-synaptic densities and post-synaptic lipid rafts. Localization of proteins within lipid rafts is highly ...

Appropriate development of nervous system connectivity involves a variety of processes, including neuronal life-and-death decisions, differentiation, axon guidance and migration, and synaptogenesis. Although these activities likely require specialized signaling events, few substrates unique to these neurotrophic functions have been identified. Here we describe the cloning of ankyrin repeat-rich...

CRE-binding protein (CREB) belongs to a family of transcription factors that mediates stimulus-dependent gene expression in neuronal and non-neuronal cells. Here we show that CREB is phosphorylated on its transcriptional regulatory site, Ser-133, in vivo in a neurotrophin-dependent manner. In mice harboring a null mutation in the Creb gene, sensory neurons exhibit excess apoptosis and degenerat...