Nanoclusters of the resting T cell antigen receptor (TCR) localize to non-raft domains

© 2014 Elsevier B.V. In the last decade an increasing number of plasma membrane (PM) proteins have been shown to be non-randomly distributed but instead forming submicron-sized oligomers called nanoclusters. Nanoclusters exist independently of the ligand-bound state of the receptors and their existence implies a high degree of lateral organisation of the PM and its proteins. The mechanisms that drive receptor nanoclustering are largely unknown. One well-defined example of a transmembrane receptor that forms nanoclusters is the T cell antigen receptor (TCR), a multisubunit protein complex whose nanoclustering influences its activity. Membrane lipids, namely cholesterol and sphingomyelin, have been shown to contribute to TCR nanoclustering. However, the identity of the membrane microdomain in which the TCR resides remains controversial. Using a GFP-labeled TCR we show here that the resting TCR localized in the disordered domain of giant PM vesicles (GPMVs) and PM spheres (PMSs) and that single and nanoclustered TCRs are found in the high-density fractions in sucrose gradients. Both findings are indicative of non-raft localization. We discuss possible mechanisms of TCR nanoclustering in T cells. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.German Research Foundation (GSC-4, the Spemann Graduate School and EXC294, the BIOSS Center for Biological Signalling Studies, by the German Research Foundation grant SCH 976/2-1, and by the European Union through grant FP7/2007-2013 SYBILLAPeer Reviewe

Interictal Photophobia and Phonophobia Are Related to the Presence of Aura and High Frequency of Attacks in Patients with Migraine

Background: Despite that photophobia and phonophobia are well-known symptoms related to migraine, it is unclear whether they affect daily life activities during the headache-free period. Objective: To evaluate the interictal photophobia/phonophobia intensity during daily activities in migraineurs and non-headache individuals. Methods: Women with migraine without aura (MoA, n = 30), migraine with aura (MA, n = 30), chronic migraine (CM, n = 30) and without headache (CG, n = 30) reported the photophobia and phonophobia intensity during daily activities using a Likert scale ranging from 0 (no discomfort) to 10 (maximum discomfort). Results: The migraine groups reported higher intensity of interictal photophobia and phonophobia than CG during “driving” and “social situations”, respectively (p < 0.05). MA and CM groups presented higher intensity of phonophobia than CG, hearing sounds in everyday situations and listening to conversations in noisy places (p < 0.05). Also, the MA group presented higher interictal phonophobia than the CG to keep concentration in noisy places (p < 0.05). Weak positive correlations were observed between the intensity of both photophobia and phonophobia with migraine intensity, frequency of migraine and frequency of aura (p < 0.05). Conclusion: Interictally, the intensity of photophobia and phonophobia reported during daily activities is higher in patients with migraine, especially those with aura and chronic migraine, than in non-headache subjects