The quantum Hall effect in two-dimensional electron gases involves the flow of topologically protected dissipationless charge currents along the edges of a sample. Integer or fractional electrical conductance is associated with edge currents of electrons or quasiparticles with fractional charges, respectively. It has been predicted that quantum Hall phenomena can also be created by edge currents with a fundamentally different origin: the fractionalization of quantum spins. However, such quantization has not yet been observed. Here we report the observation of this type of quantization of the Hall effect in an insulating two-dimensional quantum magnet, α-RuCl, with a dominant Kitaev interaction (a bond-dependent Ising-type interaction) on a two-dimensional honeycomb lattice. We find that the application of a magnetic field parallel to the sample destroys long-range magnetic order, leading to a field-induced quantum-spin-liquid ground state with substantial entanglement of local spins. In the low-temperature regime of this state, the two-dimensional thermal Hall conductance reaches a quantum plateau as a function of the applied magnetic field and has a quantization value that is exactly half of the two-dimensional thermal Hall conductance of the integer quantum Hall effect. This half-integer quantization of the thermal Hall conductance in a bulk material is a signature of topologically protected chiral edge currents of charge-neutral Majorana fermions (particles that are their own antiparticles), which have half the degrees of freedom of conventional fermions. These results demonstrate the fractionalization of spins into itinerant Majorana fermions and Z fluxes, which is predicted to occur in Kitaev quantum spin liquids. Above a critical magnetic field, the quantization disappears and the thermal Hall conductance goes to zero rapidly, indicating a topological quantum phase transition between the states with and without chiral Majorana edge modes. Emergent Majorana fermions in a quantum magnet are expected to have a great impact on strongly correlated quantum matter, opening up the possibility of topological quantum computing at relatively high temperatures.

The Kitaev quantum spin liquid displays the fractionalization of quantum spins into Majorana fermions. The emergent Majorana edge current is predicted to manifest itself in the form of a finite thermal Hall effect, a feature commonly discussed in topological superconductors. Here we report on thermal Hall conductivity κ_{xy} measurements in α-RuCl_{3}, a candidate Kitaev magnet with the two-dimensional honeycomb lattice. In a spin-liquid (Kitaev paramagnetic) state below the temperature characterized by the Kitaev interaction J_{K}/k_{B}∼80  K, positive κ_{xy} develops gradually upon cooling, demonstrating the presence of highly unusual itinerant excitations. Although the zero-temperature property is masked by the magnetic ordering at T_{N}=7  K, the sign, magnitude, and T dependence of κ_{xy}/T at intermediate temperatures follows the predicted trend of the itinerant Majorana excitations.

ABCA1 mediates release of cellular cholesterol and phospholipid to form high density lipoprotein (HDL).The three different mutants in the first extracellular domain of human ABCA1 associated with Tangier disease, R587W, W590S, and Q597R, were examined for their subcellular localization and function by using ABCA1-GFP fusion protein stably expressed in HEK293 cells. ABCA1-GFP expressed in HEK293 was fully functional for apoA-I-mediated HDL assembly. Immunostaining and confocal microscopic analyses demonstrated that ABCA1-GFP was mainly localized to the plasma membrane (PM) but also substantially in intracellular compartments. All three mutant ABCA1-GFPs showed no or little apoA-I-mediated HDL assembly. R587W and Q597R were associated with impaired processing of oligosaccharide from high mannose type to complex type and failed to be localized to the PM, whereas W590S did not show such dysfunctions. Vanadate-induced nucleotide trapping was examined to elucidate the mechanism for the dysfunction in the W590S mutant. Photoaffinity labeling of W590S with 8-azido-[␣-32 P]ATP was stimulated by adding ortho-vanadate in the presence of Mn 2؉ as much as in the presence of wildtype ABCA1. These results suggest that the defect of HDL assembly in R587W and Q597R is due to the impaired localization to the PM, whereas W590S has a functional defect other than the initial ATP binding and hydrolysis.Cholesterol is not catabolized in the peripheral cells and therefore mostly released and transported to the liver for conversion to bile acids to maintain cholesterol homeostasis. The same pathway may also remove cholesterol that has pathologically accumulated in the cells such as an initial stage of atherosclerosis. Assembly of high density lipoprotein (HDL) 1 particles by helical apolipoproteins with cellular lipid has been recognized as one of the major mechanisms for cellular cholesterol release (1, 2). The importance of this active cholesterolreleasing pathway in regulating cholesterol homeostasis became apparent by the finding that it is impaired in the cells from patients with Tangier disease, a genetic deficiency of circulating HDL (3, 4). Mutations were identified in ATP-binding cassette transporter A1 (ABCA1) of the Tangier disease (TD) patients (5-7), but the molecular mechanism of ABCA1 in the apolipoprotein-mediated HDL assembly remains unclear. Although direct interaction between ABCA1 and apoA-I at the cell surface has been suggested on the basis of chemical crosslinking experiments (8, 9), an indirect role of ABCA1 in the apoA-I binding to the cell was also proposed by a model that ABCA1 induces phosphatidylserine exofacial flopping to generate the microenvironment required for the docking of apoA-I at the cell surface (10). The predominant substrates of the ABCA1-mediated lipid release reaction are still to be determined for the HDL assembly reaction (11, 12). More than 30 mutations have been mapped in the ABCA1 gene in patients with familial hypoalphalipoproteinemia (FHA) and TD (5-7, 13-15). Many mutations have been ...

ABCA1 (ATP-binding cassette transporter A1) mediates the release of cellular cholesterol and phospholipid to form high density lipoprotein. Functions of ABCA1 are highly regulated at the transcriptional and post-transcriptional levels, and the synthesized ABCA1 protein turns over rapidly with a half-life of 1-2 h. To examine whether the functions of ABCA1 are modulated by associated proteins, a yeast two-hybrid library was screened with the C-terminal 120 amino acids of ABCA1. Two PDZ (PSD95-Discs large-ZO1) proteins, ␣1-syntrophin and Lin7, were found to interact with ABCA1. Immunoprecipitation revealed that ␣1-syntrophin interacted with ABCA1 strongly and that the interaction was via the Cterminal three amino acids SYV of ABCA1. Co-expression of ␣1-syntrophin in human embryonic kidney 293 cells retarded degradation of ABCA1 and made the half-life of ABCA1 five times longer than in the cells not expressing ␣1-syntrophin. This effect is not common among PDZcontaining proteins interacting with ABCA1, because Lin7, which was also found to interact with the C terminus region of ABCA1, did not have a significant effect on the half-life of ABCA1. Co-expression of ␣1-syntrophin significantly increased the apoA-I-mediated release of cholesterol. ABCA1 was co-immunoprecipitated with ␣1-syntrophin from mouse brain. These results suggest that ␣1-syntrophin is involved in intracellular signaling, which determines the stability of ABCA1 and modulates cellular cholesterol release.Cholesterol is not catabolized in the peripheral cells and, therefore, is mostly released and transported to the liver for conversion to bile acids to maintain cholesterol homeostasis. The same pathway may also remove cholesterol that has pathologically accumulated in cells, such as at the initial stage of atherosclerosis. The assembly of high density lipoprotein (HDL) 1 particles by lipid-free apolipoproteins with cellular lipid has been recognized as one of the major mechanisms for the cellular cholesterol release (1, 2). ApoA-I-mediated cholesterol efflux is a major event in "reverse cholesterol transport," a process that generates HDL and transports excess cholesterol from the peripheral tissues, including the arterial wall, to the liver for biliary secretion. The importance of ABCA1 in this active cholesterol-releasing pathway for regulating cholesterol homeostasis became apparent with the finding that it is impaired in the cells from patients with Tangier disease, a genetic deficiency of circulating HDL (3, 4). Tangier disease is caused by mutations in ABCA1. ABCA1 mutations are also a cause of familial HDL deficiency and are associated with premature atherosclerosis (5, 6). Cholesterol is a prerequisite for cells, but, at the same time, the hyper-accumulation of cholesterol is harmful to cells. Therefore, the expression of ABCA1 is highly regulated at both the transcriptional and post-transcriptional level. The transcription of ABCA1 is regulated by the intracellular oxysterol concentration via the LXR/RXR nuclear receptor (7), and the synt...

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