Synapse disassembly and formation of new synapses in postnatal muscle upon conditional inactivation of MuSK.

The muscle-specific-kinase MuSK is required for the formation of acetylcholine receptor clusters during embryonic development, but its physiological role in adult muscle is not known. We used the loxP/Cre system in mice to conditionally inactivate MuSK whereby expression of Cre recombinase increases during postnatal development. The MuSK-inactivated mice develop myasthenic symptoms and die prematurely due to severe muscle weakness.

Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins.

The adaptor protein (AP) 3 adaptor complex has been implicated in the transport of lysosomal membrane proteins, but its precise site of action has remained controversial. Here, we show by immuno-electron microscopy that AP-3 is associated with budding profiles evolving from a tubular endosomal compartment that also exhibits budding profiles positive for AP-1. AP-3 colocalizes with clathrin, but to a lesser extent than does AP-1.

Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells.

We conducted a genome-wide analysis of genes that are regulated by vascular endothelial growth factor (VEGF) in endothelial cells and identified DSCR1 to be most significantly induced. Consistent with an antagonistic function on calcineurin (CnA) signaling, expression of DSCR1 in endothelial cells blocked dephosphorylation, nuclear translocation, and activity of nuclear factor of activated T cell (NFAT), a transcription factor involved in mediating CnA signaling. DSCR1 was not only induced by VEGF, but also by other compounds activating CnA signaling, suggesting a more general role for DSCR1 in activated endothelial cells.

Amisyn, a novel syntaxin-binding protein that may regulate SNARE complex assembly.

The regulation of SNARE complex assembly likely plays an important role in governing the specificity as well as the timing of membrane fusion. Here we identify a novel brain-enriched protein, amisyn, with a tomosyn- and VAMP-like coiled-coil-forming domain that binds specifically to syntaxin 1a and syntaxin 4 both in vitro and in vivo, as assessed by co-immunoprecipitation from rat brain. Amisyn is mostly cytosolic, but a fraction co-sediments with membranes.