Spin-flip reflection of electrons from a potential barrier in heterostructures

Spin-conserving and spin-flip opaque reflections of electrons from a potential barrier in heterostructures are described. An electric field of the barrier is considered to be the only source of energy spin splitting in the presence of spin-orbit interaction and its form is calculated in the three-level {\kp} model for a nontrival case of unbound electrons. Reflection angles and amplitudes are calculated for oblique incoming directions. It is shown that the system can serve as a source or filter of spin-polarized electron beams. Two unexpected possibilities are pointed out: a) non attenuated electron propagation in the barrier whose height exceeds the energies of incoming electrons, b) total reflection of electrons whose energies exceed barrier's height.Comment: 10 pages, 3 figure

Theoretical model of a new type tunneling transistor

A tunneling transistor without heterojunction as a theoretical design, or more precisely controlled electron current transmission by barrier potential, is under consideration. The electrons from the conduction band of the source tunnel through the forbidden gap $E_g$ of the channel to the conduction band of the drain. The tunneling current $J$ calculations made at helium temperature for the example InAs-InAs-InAs, Au-GaSe-Au and Al-AlN-Al structures show that for a constant source-drain voltage, $V_C$, of several mV, changes in the gate voltage, $V_G$, applied to the channel within the voltage range of 0 - $E_g/$2e change $J$ by even 10 orders of magnitude. Unlike the existing solutions such as tunnel field-effect-transistor (TFET), the proposed device uses the change of $V_G$ (gate voltage), i.e. the change of the electrostatic potential in the channel, to modify the imaginary wave vector $k_z$ of tunnel current electrons. Consequently, the gate voltage controls the damping force of the electrons wave functions and thus the magnitude of the tunneling current, $J$. The effect of increasing temperature, T, on $J(V_G)$ relation was also tested. It was found that only in structures with a wide forbidden channel gap this effect is insignificant (at least up to T=300 K).Comment: 6 pages, 12 figure

Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

We previously reported that Parkinson's disease (PD) kinase LRRK2 phosphorylates a subset of Rab GTPases on a conserved residue in their switch-II domains (Steger et al., 2016) (PMID: 26824392). Here, we systematically analyzed the Rab protein family and found 14 of them (Rab3A/B/C/D, Rab5A/B/C, Rab8A/B, Rab10, Rab12, Rab29, Rab35 and Rab43) to be specifically phosphorylated by LRRK2, with evidence for endogenous phosphorylation for ten of them (Rab3A/B/C/D, Rab8A/B, Rab10, Rab12, Rab35 and Rab43). Affinity enrichment mass spectrometry revealed that the primary ciliogenesis regulator, RILPL1 specifically interacts with the LRRK2-phosphorylated forms of Rab8A and Rab10, whereas RILPL2 binds to phosphorylated Rab8A, Rab10, and Rab12. Induction of primary cilia formation by serum starvation led to a two-fold reduction in ciliogenesis in fibroblasts derived from pathogenic LRRK2-R1441G knock-in mice. These results implicate LRRK2 in primary ciliogenesis and suggest that Rab-mediated protein transport and/or signaling defects at cilia may contribute to LRRK2-dependent pathologies

A feed-forward pathway drives LRRK2 kinase membrane recruitment and activation

Activating mutations in the leucine-rich repeat kinase 2 (LRRK2) cause Parkinson’s disease, and previously we showed that activated LRRK2 phosphorylates a subset of Rab GTPases (Steger et al., 2017). Moreover, Golgi-associated Rab29 can recruit LRRK2 to the surface of the Golgi and activate it there for both auto- and Rab substrate phosphorylation. Here, we define the precise Rab29 binding region of the LRRK2 Armadillo domain between residues 360–450 and show that this domain, termed ‘site #1,’ can also bind additional LRRK2 substrates, Rab8A and Rab10. Moreover, we identify a distinct, N-terminal, higher-affinity interaction interface between LRRK2 phosphorylated Rab8 and Rab10 termed ‘site #2’ that can retain LRRK2 on membranes in cells to catalyze multiple, subsequent phosphorylation events. Kinase inhibitor washout experiments demonstrate that rapid recovery of kinase activity in cells depends on the ability of LRRK2 to associate with phosphorylated Rab proteins, and phosphorylated Rab8A stimulates LRRK2 phosphorylation of Rab10 in vitro. Reconstitution of purified LRRK2 recruitment onto planar lipid bilayers decorated with Rab10 protein demonstrates cooperative association of only active LRRK2 with phospho-Rab10-containing membrane surfaces. These experiments reveal a feed-forward pathway that provides spatial control and membrane activation of LRRK2 kinase activity

Parkinson's VPS35[D620N] mutation induces LRRK2-mediated lysosomal association of RILPL1 and TMEM55B

We demonstrate that the Parkinson's VPS35[D620N] mutation alters the expression of ~220 lysosomal proteins and stimulates recruitment and phosphorylation of Rab proteins at the lysosome. This recruits the phospho-Rab effector protein RILPL1 to the lysosome where it binds to the lysosomal integral membrane protein TMEM55B. We identify highly conserved regions of RILPL1 and TMEM55B that interact and design mutations that block binding. In mouse fibroblasts, brain, and lung, we demonstrate that the VPS35[D620N] mutation reduces RILPL1 levels, in a manner reversed by LRRK2 inhibition and proteasome inhibitors. Knockout of RILPL1 enhances phosphorylation of Rab substrates, and knockout of TMEM55B increases RILPL1 levels. The lysosomotropic agent LLOMe also induced LRRK2 kinase-mediated association of RILPL1 to the lysosome, but to a lower extent than the D620N mutation. Our study uncovers a pathway through which dysfunctional lysosomes resulting from the VPS35[D620N] mutation recruit and activate LRRK2 on the lysosomal surface, driving assembly of the RILPL1-TMEM55B complex.</p