Implications of the null mutation for synapsin phosphorylation, longevity, climbing proficiency and behavioural plasticity in adult .

The gene of encodes a highly abundant 47 kDa synaptic vesicle-associated protein. null mutants show defects in synaptic plasticity and larval olfactory associative learning but the molecular function of Sap47 at the synapse is unknown. We demonstrate that Sap47 modulates the phosphorylation of another highly abundant conserved presynaptic protein, synapsin.

The Parkinson's disease-linked Leucine-rich repeat kinase 2 (LRRK2) is required for insulin-stimulated translocation of GLUT4.

Mutations within Leucine-rich repeat kinase 2 (LRRK2) are associated with late-onset Parkinson's disease. The physiological function of LRRK2 and molecular mechanism underlying the pathogenic role of LRRK2 mutations remain uncertain. Here, we investigated the role of LRRK2 in intracellular signal transduction.

No dopamine cell loss or changes in cytoskeleton function in transgenic mice expressing physiological levels of wild type or G2019S mutant LRRK2 and in human fibroblasts.

Mutations within the LRRK2 gene have been identified in Parkinson's disease (PD) patients and have been implicated in the dysfunction of several cellular pathways. Here, we explore how pathogenic mutations and the inhibition of LRRK2 kinase activity affect cytoskeleton dynamics in mouse and human cell systems. We generated and characterized a novel transgenic mouse model expressing physiological levels of human wild type and G2019S-mutant LRRK2.

Behavioral deficits and striatal DA signaling in LRRK2 p.G2019S transgenic rats: a multimodal investigation including PET neuroimaging.

Background: A major risk-factor for developing Parkinson's disease (PD) is genetic variability in leucine-rich repeat kinase 2 (LRRK2), most notably the p.G2019S mutation. Examination of the effects of this mutation is necessary to determine the etiology of PD and to guide therapeutic development.

Characterization of peripheral hematopoietic stem cells and monocytes in Parkinson's disease.

Background: Emerging evidence has highlighted the pivotal role of the immune system in neurodegenerative diseases. This study investigated the impact of progressive neurodegeneration on the differentiation and development of hematopoietic stem cells in the peripheral blood of Parkinson's patients.

Methods: A colony-forming cell assay was established to study hematopoietic stem cells from venous blood of Parkinson's patients, and flow cytometry was used to analyze the expression of chemokine receptors on monocytes.

Behavioral and synaptic plasticity are impaired upon lack of the synaptic protein SAP47.

The synapse-associated protein of 47 kDa (SAP47) is a member of a phylogenetically conserved gene family of hitherto unknown function. In Drosophila, SAP47 is encoded by a single gene (Sap47) and is expressed throughout all synaptic regions of the wild-type larval brain; specifically, electron microscopy reveals anti-SAP47 immunogold labeling within 30 nm of presynaptic vesicles. To analyze SAP47 function, we used the viable and fertile deletion mutant Sap47(156), which suffers from a 1.

The heterogeneous nuclear ribonucleoprotein-R is necessary for axonal beta-actin mRNA translocation in spinal motor neurons.

Axonal transport and translation of beta-actin mRNA plays an important role for axonal growth and presynaptic differentiation in many neurons including hippocampal, cortical and spinal motor neurons. Several beta-actin mRNA-binding and transport proteins have been identified, including ZBP1, ZBP2 and hnRNP-R. hnRNP-R has been found as an interaction partner of the survival motor neuron protein that is deficient in spinal muscular atrophy.

The hangover gene negatively regulates bouton addition at the Drosophila neuromuscular junction.

The synaptic growth of neurons during the development and adult life of an animal is a very dynamic and highly regulated process. During larval development in Drosophila new boutons and branches are added at the glutamatergic neuromuscular junction (NMJ) until a balance between neuronal activity and morphological structures is reached. Analysis of several Drosophila mutants suggest that bouton number and size might be regulated by separate signaling processes [Budnik, V.

Differential modulation of neurite growth by the S- and the L-forms of bag1, a co-chaperone of Hsp70.

Bag1 acts as a cochaperone for Hsp70. However, it also binds to members of the RAF family and to Akt. In addition, bag1 and Hsp70 are part of a complex with glucocorticoid receptors and thus modulate glucocorticoid receptor-mediated transcriptional activation.

High-efficiency gene transfer into cultured embryonic motoneurons using recombinant lentiviruses.

Primary neurons are a common tool for investigating gene function for survival and morphological and functional differentiation. Gene transfer techniques play an important role in this context. However, the efficacy of conventional gene transfer techniques, in particular for primary motoneurons is low so that it is not possible to distinguish whether the observed effects are representative for all neurons or only for the small subpopulation that expresses the transfected cDNA.

Sox10 regulates ciliary neurotrophic factor gene expression in Schwann cells.

Ciliary neurotrophic factor (Cntf) plays an essential role in postnatal maintenance of spinal motoneurons. Whereas the expression of this neurotrophic factor is low during embryonic development, it is highly up-regulated after birth in myelinating Schwann cells of rodents. To characterize the underlying transcriptional mechanisms, we have analyzed and compared the effects of various glial transcription factors.

Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour.

Vertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been proposed to fine-regulate neurotransmitter release by phosphorylation-dependent control of synaptic vesicle motility. However, the consequences of a total lack of all synapsin isoforms due to a knock-out of all three mouse synapsin genes have not yet been investigated. In Drosophila a single synapsin gene encodes several isoforms and is expressed in most synaptic terminals.

Targeted mutagenesis of the Sap47 gene of Drosophila: flies lacking the synapse associated protein of 47 kDa are viable and fertile.

Background: Conserved proteins preferentially expressed in synaptic terminals of the nervous system are likely to play a significant role in brain function. We have previously identified and molecularly characterized the Sap47 gene which codes for a novel synapse associated protein of 47 kDa in Drosophila. Sequence comparison identifies homologous proteins in numerous species including C.