Synaptic Elimination in Neurological Disorders.

Synapses are well known as the main structures responsible for transmitting information through the release and recognition of neurotransmitters by pre- and post-synaptic neurons. These structures are widely formed and eliminated throughout the whole lifespan via processes termed synaptogenesis and synaptic pruning, respectively. Whilst the first process is needed for ensuring proper connectivity between brain regions and also with the periphery, the second phenomenon is important for their refinement by eliminating weaker and unnecessary synapses and, at the same time, maintaining and favoring the stronger ones, thus ensuring proper synaptic transmission.

Identification of new phosphorylation sites of CD23 in B-cells of patients with chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common lymphoproliferative disorder in adults. Patients with B-CLL strongly express the CD23 - C type of lectin (low affinity IgE receptor, Fc epsilon RII), which is linked to B cell activation and proliferation. Phosphorylation in lymphocytes is tightly associated with regulation of protein activities, functional regulation and cell signaling, and may thus affect initiation and/or progression of the disease.

N-type Ca channels are affected by full-length mutant huntingtin expression in a mouse model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein. In addition to facilitating neurodegeneration, mutant htt is implicated in HD-related alterations of neurotransmission. Previous data showed that htt can modulate N-type voltage-gated Ca channels (Ca2.

82-kDa choline acetyltransferase is in nuclei of cholinergic neurons in human CNS and altered in aging and Alzheimer disease.

Cholinergic neurons express choline acetyltransferase (ChAT) which synthesizes acetylcholine. We show here for the first time that primate-specific 82-kDa ChAT is expressed in nuclei of cholinergic neurons in human brain and spinal cord; isoform-specific antibodies were used to compare localization patterns and temporal expression of the more abundant 69-kDa ChAT and primate-specific 82-kDa ChAT in necropsy tissues. The 82-kDa ChAT co-localizes with 69-kDa ChAT in well-characterized cholinergic areas, but is also found in the claustrum which does not contain 69-kDa ChAT.

A model for dynamic regulation of choline acetyltransferase by phosphorylation.

Choline acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine (ACh) and is a phenotypic marker for cholinergic neurons. Cholinergic neurons in brain are involved in cognitive function, attentional processing and motor control, and decreased ChAT activity is found in several neurological disorders including Alzheimer's disease. Dysregulation of ChAT and cholinergic communication is also associated with some spontaneous point-mutations in ChAT that alter its substrate binding kinetics, or by disruption of signaling pathways that could regulate protein kinases for which ChAT is a substrate.

Surface-entropy reduction used in the crystallization of human choline acetyltransferase.

Human choline acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine (ACh) from choline and acetyl-CoA. A crystal structure of human ChAT has been a long-standing goal in the neuronal signalling field. Milligram quantities of pure ChAT can be purified [Kim et al.

Protein kinase C isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity.

Choline acetyltransferase (ChAT) synthesizes acetylcholine in cholinergic neurons; regulation of its activity or response to physiological stimuli is poorly understood. We show that ChAT is differentially phosphorylated by protein kinase C (PKC) isoforms on four serines (Ser-440, Ser-346, Ser-347, and Ser-476) and one threonine (Thr-255). This phosphorylation is hierarchical, with phosphorylation at Ser-476 required for phosphorylation at other serines.

Functional regulation of choline acetyltransferase by phosphorylation.

Choline acetyltransferase (ChAT) catalyzes synthesis of acetylcholine (ACh) in cholinergic neurons. ACh synthesis is regulated by availability of precursors choline and acetyl coenzyme A or by activity of ChAT; ChAT regulates ACh synthesis under some conditions. Posttranslational phosphorylation is a common mechanism for regulating the function of proteins.

Phosphorylation of 69-kDa choline acetyltransferase at threonine 456 in response to amyloid-beta peptide 1-42.

Choline acetyltransferase synthesizes acetylcholine in cholinergic neurons. In the brain, these neurons are especially vulnerable to effects of beta-amyloid (A beta) peptides. Choline acetyltransferase is a substrate for several protein kinases.

Beta-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization.

beta-Arrestins are important in chemoattractant receptor-induced granule release, a process that may involve Ral-dependent regulation of the actin cytoskeleton. We have identified the Ral GDP dissociation stimulator (Ral-GDS) as a beta-arrestin-binding protein by yeast two-hybrid screening and co-immunoprecipitation from human polymorphonuclear neutrophilic leukocytes (PMNs). Under basal conditions, Ral-GDS is localized to the cytosol and remains inactive in a complex formed with beta-arrestins.