Phosphorylation state of postsynaptic density proteins.

The postsynaptic density (PSD) is an electron-dense structure located at the synaptic contacts between neurons. Its considerable complexity includes cytoskeletal and scaffold proteins, receptors, ion channels and signaling molecules, in line with the role of PSDs in signal transduction and processing. The phosphorylation state of components of the PSD is central to synaptic transmission and is known to play a role in synaptic plasticity, learning and memory. The presence of a range of kinases and phosphatases in the PSD defines potential key players in this context. However, the substrates that these enzymes target have not been fully identified to date. We analyzed the protein composition of purified PSD samples from adult mouse brains by strong cation exchange chromatography fractionation of a tryptic digest followed by nano-reverse phase liquid chromatography coupled with electrospray ionization-quadrupole time of flight tandem mass spectrometry. This led to the identification of 244 proteins. To gain an insight into the phosphoproteome of the PSD we then purified phosphorylated tryptic peptides by immobilized metal ion affinity chromatography. This approach for the specific enrichment of phosphopeptides resulted in the identification of 42 phosphoproteins in the PSD preparation, 39 of which are known PSD components. Here we present a total of 83 in vivo phosphorylation sites.

[Association between membranous glomerulonephritis and Crohn's disease]. / Asociación de glomerulonefritis membranosa y enfermedad de Crohn.

We report the case of a 37 year old man who suffered from Crohn's Disease (CD), and was receiving treatment with mesalazine (5-ASA). Nine years after the diagnosis, because of detecting a slight proteinuria, a renal biopsy is made, being the anatomo-pathologic result compatible with membranous glomerulonephritis (MGN). Checking previous literature we have only found two cases reported of MGN in coincidence with Inflammatory Bowel Disease (IBD), one in association with Ulcerative Colitis and the other with Crohn's Disease in a 12 years old boy. This is, therefore, the second case presenting MGN associated with CD and the first in an adult patient.

Asociación de glomerulonefritis membranosa y Enfermedad de Crohn / Association between membranous glomerulonephritis and Crohn's disease

Describimos el caso de un paciente varón de 37 años diagnosticado de Enfermedad de Crohn (EC), en tratamiento con Mesalazina (5-ASA). Nueve años después del diagnóstico se realiza biopsia renal por presentar proteinuria ligera, siendo el resultado anatomopatológico compatible con glomerulonefritis membranosa (GNM).Revisando la bibliografía se han descrito anteriormente dos casos de GNM asociada con enfermedad inflamatoria intestinal (EII): uno asociado con colitis ulcerosa (CU) y otro con EC en un paciente de 12 años. Nuestro caso, por tanto, sería el segundo con GNM asociada con EC y el primero en un paciente de edad adulta (AU)

The Agrin/MuSK signaling pathway is spatially segregated from the neuregulin/ErbB receptor signaling pathway at the neuromuscular junction.

The neuregulin/erbB receptor and agrin/MuSK pathways are critical for communication between the nerve, muscle, and Schwann cell that establishes the precise topological arrangement at the vertebrate neuromuscular junction (NMJ). ErbB2, erbB3, and erbB4 as well as neuregulin, agrin, and MuSK are known to be concentrated at the NMJ. Here we have examined NMJs from gastrocnemius muscle of adult rat using immunofluorescence confocal microscopy to characterize in detail the distribution of these proteins relative to the distribution of acetylcholine receptors (AChRs). We have determined that erbB2 and erbB4 are enriched in the depths of the secondary junctional folds on the postsynaptic muscle membrane. In contrast, erbB3 at the NMJ was concentrated at presynaptic terminal Schwann cells. This distribution strongly argues that erbB2/erbB4 heterodimers are the functional postsynaptic neuregulin receptors of the NMJ. Neuregulin was localized to the axon terminal, secondary folds, and terminal Schwann cells, where it was in a position to signal through erbB receptors. MuSK was concentrated in the postsynaptic primary gutter region where it was codistributed with AChRs. Agrin was present at the axon terminal and in the basal lamina associated with the primary gutter region, but not in the secondary junctional folds. The differential distributions of the neuregulin and agrin signaling pathways argue against neuregulin and erbB receptors being localized to the NMJ via direct interactions with either agrin or MuSK.

[Tuberous sclerosis. Description of a family study]. / Esclerosis tuberosa. Descripción de un estudio familiar.

We present tuberous sclerosis affecting all the members of a family, now and for three consecutive generations (probably four). A fortuitous study of cutaneous disease in one member led to diagnosis in all of them. A systematic study detected important visceral implication in all cases, mainly neurological, despite the fact only one of then showed related symptoms. We discuss the epidemiological and diagnostic aspects of an illness, which is widely underdiagnosed even today, despite the fact that detection is by sight.