Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2.

The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its endosomal sorting.

Retromer Controls Planar Polarity Protein Levels and Asymmetric Localization at Intercellular Junctions.

The coordinated polarization of cells in the plane of a tissue, termed planar polarity, is a characteristic feature of epithelial tissues [1]. In the fly wing, trichome positioning is dependent on the core planar polarity proteins adopting asymmetric subcellular localizations at apical junctions, where they form intercellular complexes that link neighboring cells [1-3]. Specifically, the seven-pass transmembrane protein Frizzled and the cytoplasmic proteins Dishevelled and Diego localize to distal cell ends, the four-pass transmembrane protein Strabismus and the cytoplasmic protein Prickle localize proximally, and the seven-pass transmembrane spanning atypical cadherin Flamingo localizes both proximally and distally.

Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo.

Abnormal alpha-synuclein (α-synuclein) expression and aggregation is a key characteristic of Parkinson's disease (PD). However, the exact mechanism(s) linking α-synuclein to the other central feature of PD, dopaminergic neuron loss, remains unclear. Therefore, improved cell and in vivo models are needed to investigate the role of α-synuclein in dopaminergic neuron loss.

The emerging role of retromer in neuroprotection.

Efficient sorting and transportation of integral membrane proteins, such as ion channels, nutrient transporters, signalling receptors, cell-cell and cell-matrix adhesion molecules is essential for the function of cellular organelles and hence organism development and physiology. Retromer is a master controller of integral membrane protein sorting and transport through one of the major sorting station within eukaryotic cells, the endosomal network. Subtle de-regulation of retromer is an emerging theme in the pathoetiology of Parkinson's disease.

Atypical parkinsonism-associated retromer mutant alters endosomal sorting of specific cargo proteins.

The retromer complex acts as a scaffold for endosomal protein complexes that sort integral membrane proteins to various cellular destinations. The retromer complex is a heterotrimer of VPS29, VPS35, and VPS26. Two of these paralogues, VPS26A and VPS26B, are expressed in humans.

Burnout and the provision of psychosocial care amongst Australian cancer nurses.

Purpose: To assess the prevalence of burnout amongst Australian cancer nurses as well as investigate the systemic and individual factors associated with burnout, including training and supervision for nurses in psychosocial care. Burnout amongst cancer nurses can have serious consequences for the individual nurse, the hospital and patients. Psychosocial care has been demonstrated in many studies to reduce distress in cancer patients; however, previous studies have suggested that providing psychosocial care can be stressful if nurses feel they lack appropriate training.

Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation.

Retromer is a protein assembly that plays a central role in orchestrating export of transmembrane-spanning cargo proteins from endosomes into retrieval pathways destined for the Golgi apparatus and the plasma membrane [1]. Recently, a specific mutation in the retromer component VPS35, VPS35(D620N), has linked retromer dysfunction to familial autosomal dominant and sporadic Parkinson disease [2, 3]. However, the effect of this mutation on retromer function remains poorly characterized.