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1.
Proc Natl Acad Sci U S A ; 107(36): 15780-5, 2010 Sep 07.
Article in English | MEDLINE | ID: mdl-20798032

ABSTRACT

Two profilin isoforms (PFN1 and PFN2a) are expressed in the mammalian brain. Although profilins are essential for regulating actin dynamics in general, the specific role of these isoforms in neurons has remained elusive. We show that knockdown of the neuron-specific PFN2a results in a significant reduction in dendrite complexity and spine numbers of hippocampal neurons. Overexpression of PFN1 in PFN2a-deficient neurons prevents the loss of spines but does not restore dendritic complexity. Furthermore, we show that profilins are involved in differentially regulating actin dynamics downstream of the pan-neurotrophin receptor (p75(NTR)), a receptor engaged in modulating neuronal morphology. Overexpression of PFN2a restores the morphological changes in dendrites caused by p75(NTR) overexpression, whereas PFN1 restores the normal spine density. Our data assign specific functions to the two PFN isoforms, possibly attributable to different affinities for potent effectors also involved in actin dynamics, and suggest that they are important for the signal-dependent fine-tuning of neuronal architecture.


Subject(s)
Neurons/cytology , Profilins/physiology , Protein Isoforms/physiology , Animals , Base Sequence , Gene Knockdown Techniques , Immunohistochemistry , Mice , Profilins/genetics , Protein Isoforms/genetics , RNA Interference , Signal Transduction
2.
Eur J Neurosci ; 32(2): 218-23, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20646046

ABSTRACT

During brain maturation, neurons form specific connections with each other to establish functional neuronal circuits. The processes underlying the development of connectivity, such as the selection of synaptic partners and the fine-tuning of neuronal networks, act with single-synapse precision. Calcium is an intracellular secondary messenger that operates with remarkable spatio-temporal specificity and regulates functional and structural adaptations at the level of individual synapses. Although the structure, molecular composition and function of an emerging synapse changes dramatically during its development, the single-synapse specificity of calcium signaling is maintained at every step of synapse formation: when the first contacts between axons and dendrites form, during the onset of synaptic function and later, when spine synapses emerge. Here, we describe the mechanisms that help developing neurons to confine calcium signaling to individual synapses, and discuss how these local calcium dynamics facilitate the development of accurate neuronal connections at each step of synapse maturation.


Subject(s)
Brain/growth & development , Calcium Signaling/physiology , Neurogenesis/physiology , Synapses/metabolism , Animals , Brain/metabolism , Humans
3.
FEMS Microbiol Lett ; 271(2): 251-7, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17439544

ABSTRACT

Members of the genus Prochlorococcus belong to the most abundant phytoplankton on earth. In contrast to other cyanobacteria, Prochlorococcus is characterized by divinyl-chlorophyll containing light-harvesting complexes and the lack of phycobilisomes. Despite the lack of phycobilisomes, all sequenced genomes of Prochlorococcus possess genes that putatively encode enzymes involved in the biosynthesis of open-chain tetrapyrrole molecules. Here, biochemical evidence is presented indicating that high-light- and low-light-adapted Prochlorococcus ecotypes possess genes encoding functional enzymes for the biosynthesis of open-chain tetrapyrrole molecules. Experiments on recombinant protein as well as through complementation studies of a cyanobacterial insertion mutant revealed the functionality of the bilin reductases investigated.


Subject(s)
Prochlorococcus/metabolism , Tetrapyrroles/biosynthesis , Bile Pigments/biosynthesis , Bile Pigments/chemistry , Chromatography, High Pressure Liquid , Genetic Complementation Test , Light , Light-Harvesting Protein Complexes/biosynthesis , Light-Harvesting Protein Complexes/chemistry , Models, Biological , Molecular Structure , Mutation , Oxidoreductases/genetics , Oxidoreductases/metabolism , Phycoerythrin/biosynthesis , Phycoerythrin/chemistry , Phylogeny , Plasmids/genetics , Prochlorococcus/genetics , Prochlorococcus/radiation effects , Recombinant Proteins/metabolism , Spectrophotometry , Tetrapyrroles/chemistry
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