During the formation of neuronal circuits, afferent axons often enter target regions before their target cells are mature and then make temporary contacts with nonspecific targets before forming synapses on specific target cells. The regulation of these different steps of afferent-target interactions is poorly understood. The cerebellum is a good model for addressing these aspects, because cere...

The roles of the intracellular calcium pool involved in regulating the Ca2+ profile and the neuronal survival rate during development were studied by using thapsigargin (TG), a specific inhibitor of endoplasmic reticulum (ER) Ca2+-ATPase in cultured cerebellar granule neurons. Measuring the neuronal [Ca2+]i directly in the culture medium, we found a bell-shaped curve for [Ca2+]i versus cultured...

The molecular mechanisms that regulate membrane targeting/fusion during platelet granule secretion are not yet understood. N-ethylmaleimide-sensitive fusion protein (NSF), soluble NSF attachment proteins (SNAPs), and SNAREs (SNAP receptors) are elements of a conserved molecular machinery for membrane targeting/fusion that have been detected in platelets. We examined whether NSF, an ATPase that ...

Jiang Tang Xiao Ke (JTXK) granule, a Chinese herbal formula, has been used clinically to treat type 2 diabetes (T2DM) for decades. Our previous studies showed that JTXK granule exhibited anti-diabetic and anti-oxidative functions in experimental diabetic rats induced by a high fat diet and streptozotocin. However, the underlying mechanisms remain poorly understood. Herein, we aimed to investiga...

Human neutrophils are filled with intracellular storage organelles, called granules and secretory vesicles, which differ in their content of soluble matrix proteins and membrane-bound molecules. To date, at least four distinct granule/vesicle subsets have been identified. These organelles may secrete their content extracellularly following mobilization to and fusion with the plasma membrane, bu...

We have studied the time course of migratory behavior of cerebellar granule cells in the microwell tissue culture system. [3H]Thymidine served as a marker for particular granule cell generations. When cultured 4 hr after [3H]thymidine injection for 6 days in microwell cultures, labeled granule cells were seen to migrate along fiber bundles expanding between reaggregates called "cables" for 3 to...

The primary cilium, a sensory organelle, regulates cell proliferation and neuronal development of dentate granule cells in the hippocampus. However, its role in the function of mature dentate granule cells remains unknown. Here we specifically depleted and disrupted ciliary proteins IFT20 and Kif3A (respectively) in mature dentate granule cells and investigated hippocampus-dependent contextual ...

by a short BrdU pulse, indicating that prevention of Bmi1 downregulation does not drive granule cells back into the cell cycle. No tumours were observed in two aging cohorts of transgenic mice derived from separate founder lines. However, these mice display an increase in astrocytes with the type II morphology in vitro compared to wild-type littermates. Cultures of FACSorted Math1-GFP+ granule ...

The weaver mutation results in the extensive death of midline cerebellar granule cells. The mutation consists of a single base pair substitution of the gene encoding the G-protein-activated inwardly rectifying potassium channel protein, GIRK2. The functional consequences of this mutation are still in dispute. In this study we demonstrate the in vivo and in vitro rescue of weaver granule cells w...

In the neurological mutant mouse weaver, granule cell precursors proliferate normally in the external germinal layer of the cerebellar cortex, but fail to differentiate. Granule neurons purified from weaver cerebella have greatly reduced G protein-activated inwardly rectifying K+ currents; instead, they display a constitutive Na+ conductance. Expression of the weaver GIRK2 channel in oocytes co...