Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing

sorLA is a sorting receptor for amyloid precursor protein (APP) genetically linked to Alzheimer's disease (AD). Retromer, an adaptor complex in the endosome-to-Golgi retrieval pathway, has been implicated in APP transport because retromer deficiency leads to aberrant APP sorting and processing and levels of retromer proteins are altered in AD. Here we report that sorLA and retromer functionally interact in neurons to control trafficking and amyloidogenic processing of APP. We have identified a sequence (FANSHY) in the cytoplasmic domain of sorLA that is recognized by the VPS26 subunit of the retromer complex. Accordingly, we characterized the interaction between the retromer complex and sorLA and determined the role of retromer on sorLA-dependent sorting and processing of APP. Mutations in the VPS26 binding site resulted in receptor redistribution to the endosomal network, similar to the situation seen in cells with VPS26 knockdown. The sorLA mutant retained APP-binding activity but, as opposed to the wild-type receptor, misdirected APP into a distinct non-Golgi compartment, resulting in increased amyloid processing. In conclusion, our data provide a molecular link between reduced retromer expression and increased amyloidogenesis as seen in patients with sporadic AD

Secretion of five extracellular enzymes by strains of chromoblastomycosis agents Secreção de cinco enzimas extracelulares por amostras de agentes da cromoblastomicose

The gelatinase, urease, lipase, phospholipase and DNase activities of 11 chromoblastomycosis agents constituted by strains of Fonsecaea pedrosoi, F. compacta, Phialophora verrucosa, Cladosporium carrionii, Cladophialophora bantiana and Exophiala jeanselmei were analyzed and compared. All strains presented urease, gelatinase and lipase activity. Phospholipase activity was detected only on five of six strains of F. pedrosoi. DNase activity was not detected on the strains studied. Our results indicate that only phospholipase production, induced by egg yolk substrate, was useful for the differentiation of the taxonomically related species studied, based on their enzymatic profile.<br>As atividades gelatinase, urease, lipase, fosfolipase e DNase de 11 agentes da cromoblastomicose constituídos por amostras de Fonsecaea pedrosoi, F. compacta, Phialophora verrucosa, Cladosporium carrionii, Cladophialophora bantiana e Exophiala jeanselmei foram analisadas e comparadas. Todas as amostras apresentaram atividade urease, gelatinase e lipase. A atividade fosfolipase foi detectada apenas em cinco das seis amostras de F. pedrosoi. A atividade DNase não foi detectada nas amostras estudadas. Os resultados indicam que para a diferenciação entre espécies taxonomicamente relacionadas estudadas, baseado no seu perfil enzimático, apenas a produção de fosfolipase, induzida pelo substrato com gema de ovo, foi útil

Sex, gender, and decisions at the family -> work interface

What is the linkage between individuals’ sex and the interface between their work and family roles? The answer to this question is by no means straightforward as gender roles, work roles, and family roles evolve. To address the question, the authors examine the influence of family-domain factors on work-domain decisions and their linkages to sex and gender. According to the logic of appropriateness, a theory of decision making, people develop and apply rules in decision-making situations that are consistent with their personal identities. The authors identify three broad types of decisions in the work domain—role entry, participation, and exit decisions—that may be influenced by factors in the family domain according to such rules. Next, they review the literature on the linkage between individuals’ sex and an example of each of these types of decisions: the role entry decision about whether to start a business, the role participation decision about the number of hours to devote to one’s job or business, and the role exit decision about whether to quit a job. The review suggests that (a) family-domain factors mediate effects of sex on work-domain decisions and (b) sex moderates relationships between family-domain factors and work-domain decisions. Based on the review, the authors offer a model of the linkages among sex, family-domain factors, and work-domain decisions that incorporates constructs from theories of the psychology of gender (femininity) and identity theories (family role salience). Finally, the authors offer guidelines for future theory and research to test and extend the model