Disruption of Spectrin-Like Cytoskeleton in Differentiating Keratinocytes by PKCδ Activation Is Associated with Phosphorylated Adducin

Spectrin is a central component of the cytoskeletal protein network in a variety of erythroid and non-erythroid cells. In keratinocytes, this protein has been shown to be pericytoplasmic and plasma membrane associated, but its characteristics and function have not been established in these cells. Here we demonstrate that spectrin increases dramatically in amount and is assembled into the cytoskeleton during differentiation in mouse and human keratinocytes. The spectrin-like cytoskeleton was predominantly organized in the granular and cornified layers of the epidermis and disrupted by actin filament inhibitors, but not by anti-mitotic drugs. When the cytoskeleton was disrupted PKCδ was activated by phosphorylation on Thr505. Specific inhibition of PKCδ(Thr505) activation with rottlerin prevented disruption of the spectrin-like cytoskeleton and the associated morphological changes that accompany differentiation. Rottlerin also inhibited specific phosphorylation of the PKCδ substrate adducin, a cytoskeletal protein. Furthermore, knock-down of endogenous adducin affected not only expression of adducin, but also spectrin and PKCδ, and severely disrupted organization of the spectrin-like cytoskeleton and cytoskeletal distribution of both adducin and PKCδ. These results demonstrate that organization of a spectrin-like cytoskeleton is associated with keratinocytes differentiation, and disruption of this cytoskeleton is mediated by either PKCδ(Thr505) phosphorylation associated with phosphorylated adducin or due to reduction of endogenous adducin, which normally connects and stabilizes the spectrin-actin complex

The awakening of BL Lacertae: observations by Fermi, Swift and the GASP-WEBT

Since the launch of the Fermi satellite, BL Lacertae has been moderately active at gamma-rays and optical frequencies until 2011 May, when the source started a series of strong flares. The exceptional optical sampling achieved by the GLAST-AGILE Support Program of the Whole Earth Blazar Telescope in collaboration with the Steward Observatory allows us to perform a detailed comparison with the daily gamma-ray observations by Fermi. Discrete correlation analysis between the optical and gamma-ray emission reveals correlation with a time lag of 0 +/- 1 d, which suggests cospatiality of the corresponding jet emitting regions. A better definition of the time lag is hindered by the daily gaps in the sampling of the extremely fast flux variations. In general, optical flares present more structure and develop on longer time-scales than corresponding gamma-ray flares. Observations at X-rays and at millimetre wavelengths reveal a common trend, which suggests that the region producing the mm and X-ray radiation is located downstream from the optical and gamma-ray-emitting zone in the jet. The mean optical degree of polarization slightly decreases over the considered period and in general it is higher when the flux is lower. The optical electric vector polarization angle (EVPA) shows a preferred orientation of about 15 degrees, nearly aligned with the radio core EVPA and mean jet direction. Oscillations around it increase during the 2011-2012 outburst. We investigate the effects of a geometrical interpretation of the long-term flux variability on the polarization. A helical magnetic field model predicts an evolution of the mean polarization that is in reasonable agreement with the observations. These can be fully explained by introducing slight variations in the compression factor in a transverse shock waves model

Two mechanisms regulate keratin K15 expression in keratinocytes:role of PKC/AP-1 and FOXM1 mediated signalling

PMCID: PMC3384677This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Keratin 15 (K15) is a type I keratin that is used as a marker of stem cells. Its expression is restricted to the basal layer of stratified epithelia, and the bulge in hair follicles. However, in certain clinical situations including oral lichen planus, K15 is induced in suprabasal layers, which is inconsistent with the role of a stem cell marker. This study provides insights into the mechanisms of K15 expression in the basal and differentiating keratinocytes