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In humans, loss‐of‐function mutations of Kcnj10 in SeSAME/EAST syndrome, which encodes the inwardly rectifying K+ channel 4.1 (Kir4.1), causes progressive neurological decline. Despite its rich expression in oligodendrocyte (OL) lineage cells and an emerging link with demyelinating disease, the function of Kir4.1 in OLs is unclear. Here we show a novel role of Kir4.1 in OL development. Kir4.1 expression...
Oligodendrocytes are generated by the differentiation and maturation of oligodendrocyte precursor cells (OPCs). The failure of OPC differentiation is a major cause of demyelinating diseases; thus, identifying the molecular mechanisms that affect OPC differentiation is critical for understanding the myelination process and repairing after demyelination. Although prevailing evidence shows that OPC differentiation...
Excessive extracellular glutamate leads to neuronal death in central nervous system. Excitatory glutamate transporter subtype 2 (GLT‐1) carries bulk of glutamate reuptake in cerebral ischemia. Although GLT‐1 expression fluctuates during the period of ischemia, little is known about its regulatory mechanism. Here we show an up‐regulation of GLT‐1 via mammalian target of rapamycin (mTOR)‐Akt‐nuclear...
Neurons critically depend on the long‐distance transport of mitochondria. Motor proteins kinesin and dynein control anterograde and retrograde mitochondrial transport, respectively in axons. The regulatory molecules that link them to mitochondria need to be better characterized. Nuclear distribution (Nud) family proteins LIS1, Ndel1 and NudCL are critical components of cytoplasmic dynein complex. Roles of these Nud proteins in neuronal mitochondrial transport are unknown. Here we report distinct functions of LIS1, Ndel1 and NudCL on axonal mitochondrial transport in cultured hippocampal neurons. We found that LIS1 interacted with kinsein family protein KIF5b. Depletion of LIS1 enormously suppressed mitochondrial motility in both anterograde and retrograde directions. Inhibition of either Ndel1 or NudCL only partially reduced retrograde mitochondrial motility. However, knocking down both Ndel1 and NudCL almost blocked retrograde mitochondrial transport, suggesting these proteins may work together to regulate retrograde mitochondrial transport through linking dynein‐LIS1 complex. Taken together, our results uncover novel roles of LIS1, Ndel1 and NudCL in the transport of mitochondria in axons....
Ionotropic glutamate receptors (iGluRs) are expressed in islets and insulinoma cells and involved in insulin secretion. However, the exact roles that iGluRs play in β cells remain unclear. Here, we demonstrated that GluR2‐containing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors (AMPARs) were expressed in mouse β cells. Glutamate application increased both cytosolic calcium and the...
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