Author:
Porciello Nicla,Cipria Deborah,Masi Giulia,Lanz Anna-Lisa,Milanetti Edoardo,Grottesi Alessandro,Howie Duncan,Cobbold Steve P.,Schermelleh Lothar,He Hai-Tao,D’Abramo Marco,Destainville Nicolas,Acuto Oreste,Nika Konstantina
Abstract
AbstractTheoretical work suggests that collective spatiotemporal behaviour of integral membrane proteins (IMPs) can be modulated by annular lipids sheathing their hydrophobic moiety. Here, we present evidence for this prediction in a natural membrane by investigating the mechanism that maintains steady amount of active isoform of Lck kinase (LckA) by Lck trans-autophosphorylation offset by the phosphatase CD45. We gauged experimental suitability by quantitation of CD45 and LckAsubcellular localisation, LckAgeneration as a function of Lck and pharmacological perturbation. Steady LckAwas challenged by swapping Lck membrane anchor with structurally divergent ones expected to substantially modify Lck annular lipids, such as that of Src or the transmembrane domains of LAT, CD4, palmitoylation-defective CD4 and CD45, respectively. The data showed only small alteration of LckA, except for CD45 hydrophobic anchor that thwarted LckA, due to excessive lateral proximity to CD45. The data are best explained by annular lipids facilitating or penalising IMPs’ lateral proximity, hence modulating IMPs protein-protein functional interactions. Our findings can contribute to improve the understanding of biomembranes’ organisation.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献