Protein Kinase D Regulates the Fission of Cell Surface Destined Transport Carriers from the Trans-Golgi Network

AbstractWhen a kinase inactive form of Protein Kinase D (PKD-K618N) was expressed in HeLa cells, it localized to the trans-Golgi network (TGN) and caused extensive tubulation. Cargo that was destined for the plasma membrane was found in PKD-K618N-containing tubes but the tubes did not detach from the TGN. As a result, the transfer of cargo from TGN to the plasma membrane was inhibited. We have also demonstrated the formation and subsequent detachment of cargo-containing tubes from the TGN in cells stably expressing low levels of PKD-K618N. Our results suggest that PKD regulates the fission from the TGN of transport carriers that are en route to the cell surface

220th ENMC workshop: Dystroglycan and the dystroglycanopathies Naarden, The Netherlands, 27–29 May 2016

Highlights • Review of clinical phenotypes associated with the dystroglycanopathies. • Discussion of current animal models and their contribution to understanding the disease process. • New insight into the glycosylation of alpha dystroglycan and the role of LARGE. • Structural information on the LARGE glycan

Efficacy and safety of proactive treatment with twice-weekly topical Cal/BD foam in patients with plaque psoriasis undergoing HPA-axis testing: a PSO-LONG subgroup analysis

Objective In PSO-LONG, long-term proactive management (PAM) of psoriasis with fixed-dose combination calcipotriol 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) aerosol foam was superior to conventional reactive management. This post-hoc analysis investigated long-term PAM with Cal/BD foam in PSO-LONG patients who could be more susceptible to corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression. Methods Efficacy and safety of PAM with Cal/BD foam (twice-weekly) versus reactive management (twice-weekly vehicle foam), with once-daily rescue Cal/BD foam for four weeks following relapse, was assessed in the HPA subgroup (n = 66); patients had moderate-to-severe psoriasis (physician global assessment score ≥3; 10–30% body surface area affected). Primary endpoint was time to first relapse. Results PAM with Cal/BD foam was associated with longer median time to first relapse (111 versus 31 days), reduced risk of first relapse (hazard ratio: 0.49; p = .029), greater proportion of days in remission (17%; p = .001) and reduced rate of relapse (60% reduction; p < .001) than reactive management. Adverse events occurred in 37.5% (PAM) and 47.1% (reactive management) of patients, with no new safety signals. No clinically significant HPA-axis suppression was observed. Conclusion Efficacy of PAM with Cal/BD foam is maintained in patients with moderate-to-severe psoriasis, with no new safety signals