TY - JOUR
T1 - Influence of intracellular membrane pH on sphingolipid organization and membrane biophysical properties
AU - Varela, Ana R.P.
AU - Gonçalves Da Silva, Amélia M.P.S.
AU - Fedorov, Alexander
AU - Futerman, Anthony H.
AU - Prieto, Manuel
AU - Silva, Liana C.
N1 - Fundacao para a Ciencia e Tecnologia (FCT), Portugal [PTDC/QUI-BIQ/111411/2009]; FCT [SFRH/BD/69982/2010]; Compromisso para a Ciencia from FCTWe are grateful for discussions with Professor Samuel Safran of the Weizmann Institute of Science. This work was supported by PTDC/QUI-BIQ/111411/2009 from Fundacao para a Ciencia e Tecnologia (FCT), Portugal. FCT provided a research grant to A .R. P.V. (SFRH/BD/69982/2010). L.C.S. acknowledges funding from Compromisso para a Ciencia 2008 from FCT. A.H.F. is The Joseph Meyerhoff Professor of Biochemistry at the Weizmann Institute of Science.
PY - 2014/4/15
Y1 - 2014/4/15
N2 - Glucosylceramide (GlcCer) is a signaling lipid involved in the regulation of several cellular processes. It is present in different organelles, including the plasma membrane, Golgi apparatus, endoplasmic reticulum, and lysosomes. Accordingly, GlcCer is exposed to different pH environments in each organelle, which may lead to alterations in its properties and lateral organization and subsequent biological outcome. In this study, we addressed the effect of pH on the biophysical behavior of this lipid and other structurally related sphingolipids (SLs). Membranes composed of POPC (1-palmitoyl-2-oleoyl-sn- glycero-3-phosphocholine) and C16-GlcCer, sphingomyelin, and different acyl chain ceramides were characterized by fluorescence spectroscopy, confocal microscopy, and surface pressure-area measurements under neutral and acidic conditions. The results show that changing the pH from 7.4 to 5.5 has a larger impact on C16-GlcCer-containing membranes compared to other SLs. In addition, acidification mainly affects the organization and packing properties of the GlcCer-enriched gel phase, suggesting that the interactions established by the glucose moiety, in the GlcCer molecule, are those most affected by the increase in the acidity. These results further highlight the role of GlcCer as a modulator of membrane biophysical properties and will possibly contribute to the understanding of its biological function in different organelles.
AB - Glucosylceramide (GlcCer) is a signaling lipid involved in the regulation of several cellular processes. It is present in different organelles, including the plasma membrane, Golgi apparatus, endoplasmic reticulum, and lysosomes. Accordingly, GlcCer is exposed to different pH environments in each organelle, which may lead to alterations in its properties and lateral organization and subsequent biological outcome. In this study, we addressed the effect of pH on the biophysical behavior of this lipid and other structurally related sphingolipids (SLs). Membranes composed of POPC (1-palmitoyl-2-oleoyl-sn- glycero-3-phosphocholine) and C16-GlcCer, sphingomyelin, and different acyl chain ceramides were characterized by fluorescence spectroscopy, confocal microscopy, and surface pressure-area measurements under neutral and acidic conditions. The results show that changing the pH from 7.4 to 5.5 has a larger impact on C16-GlcCer-containing membranes compared to other SLs. In addition, acidification mainly affects the organization and packing properties of the GlcCer-enriched gel phase, suggesting that the interactions established by the glucose moiety, in the GlcCer molecule, are those most affected by the increase in the acidity. These results further highlight the role of GlcCer as a modulator of membrane biophysical properties and will possibly contribute to the understanding of its biological function in different organelles.
UR - http://www.scopus.com/inward/record.url?scp=84898879727&partnerID=8YFLogxK
U2 - 10.1021/la5003397
DO - 10.1021/la5003397
M3 - مقالة
SN - 0743-7463
VL - 30
SP - 4094
EP - 4104
JO - Langmuir
JF - Langmuir
IS - 14
ER -