Phospholipids undergo hop diffusion in compartmentalized cell membrane

Fujiwara, Takeshi; Ritchie, Ken; Murakoshi, Hideji; Jacobson, Ken; Kusumi, Akihiro

doi:10.1083/jcb.200202050

Cited by 877 publications

(1,137 citation statements)

References 40 publications

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“…Although our effective diffusion coefficients were somewhat larger, we attribute this to differences in experimental setup, diffusion models, and fitting routines, since our reported D values for di-8-ANEPPS diffusion in HEKs and OHCs were similar. All values are within the range typically reported for macroscopic effective diffusion coefficients in cell membranes, on the order of 10 −8 to 10 −9 cm 2 /s (Edidin 1987;Fujiwara et al 2002). However, comparisons of quantitative mobility parameters showed distinct differences in lateral mobility between OHC regions.…”

Section: Discussionsupporting

confidence: 81%

Lipid Lateral Mobility in Cochlear Outer Hair Cells: Regional Differences and Regulation by Cholesterol

Organ

Raphael

2009

JARO

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The outer hair cell (OHC) lateral plasma membrane houses the transmembrane protein prestin, a necessary component of the yet unknown molecular mechanism (s) underlying electromotility and the exquisite sensitivity and frequency selectivity of mammalian hearing. The importance of the plasma membrane environment in modulating OHC electromotility has been substantiated by recent studies demonstrating that membrane cholesterol alters prestin activity in a manner consistent with cholesterol-induced changes in auditory function. Cholesterol is known to affect membrane material properties, and measurements of lipid lateral mobility provide a method to asses these changes in living OHCs. Using fluorescence recovery after photobleaching (FRAP), we characterized regional differences in the lateral diffusion of the lipid analog di-8-ANEPPS in OHCs and investigated whether lipid mobility, which reflects membrane fluidity, is sensitive to membrane cholesterol. FRAP experiments revealed quantitative differences in lipid lateral mobility among the apical, lateral, and basal regions of the OHC and demonstrated that diffusion in individual regions is uniquely sensitive to cholesterol manipulations. Interestingly, in the lateral region, both cholesterol depletion and loading significantly reduced the effective diffusion coefficient from control values. Thus, the fluidity of the OHC lateral plasma membrane is regulated by cholesterol levels in a non-monotonic manner, suggesting that the overall material properties of the lateral plasma membrane are optimally tuned for OHC function in the native state. These results support the idea that the cholesteroldependent regulation of prestin function and electromotility correlates with changes in the properties of the lipid environment that surrounds and supports prestin.

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Section: Discussionsupporting

confidence: 81%

Lipid Lateral Mobility in Cochlear Outer Hair Cells: Regional Differences and Regulation by Cholesterol

Organ

Raphael

2009

JARO

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“…This is thought to occur due to the steric hindrance imposed by the cytoskeleton on the cytoplasmic domains of these proteins. Treatment of cells with agents that disrupt the cytoskeleton [38], truncation of the cytoplasmic domains of transmembrane proteins [39], or a lack of interaction of membrane proteins with cytoplasmic effector molecules [40] tends to increase their mobility on the cell surface. Likewise, the presence of the bulky heterotrimeric G-protein complex associated with the receptor (since Gproteins, when bound to membrane receptors, could be considered as equivalent to cytoplasmic domains of membrane proteins) could further reduce (over the differences arising due to molecular mass of G-proteins) receptor diffusion, which would be partially relieved when the Gprotein dissociates from the receptor.…”

Section: Discussionmentioning

confidence: 99%

The human serotonin1A receptor exhibits G-protein-dependent cell surface dynamics

Pucadyil

Chattopadhyay

2006

Glycoconj J

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Seven transmembrane domain G-protein-coupled receptors constitute the largest family of proteins in mammals. Signal transduction events mediated by such receptors are the primary means by which cells communicate with and respond to their external environment. The major paradigm in this signal transduction process is that stimulation of the receptor leads to the recruitment and activation of heterotrimeric GTP-binding proteins. These initial events, which are fundamental to all types of G-protein-coupled receptor signaling, occur at the plasma membrane via protein-protein interactions. As a result, the dynamics of the activated receptor on cell surfaces represents an important determinant in its encounter with G-proteins, and has significant impact on the overall efficiency of the signal transduction process. We have monitored the cell surface dynamics of the serotonin 1A receptor, an important member of the G-protein-coupled receptor superfamily, in relation to its interaction with G-proteins. Fluorescence recovery after photobleaching experiments carried out with the receptor tagged to the enhanced yellow fluorescent protein indicate that G-protein activation alters the diffusion properties of the receptor in a manner suggesting the activation process leads to dissociation of G-proteins from the receptor. This result demonstrates that the cell surface dynamics of the serotonin 1A receptor is modulated in a G-protein-dependent manner. Importantly, this result could provide the basis for a sensitive and powerful approach to assess receptor/ G-protein interaction in an intact cellular environment.

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“…• Kusumi and colleagues have shown that the plasma membrane is compartmentalized by a picket fence of transmembrane proteins that are anchored to the submembrane actin cytoskeleton 26,[67][68][69] . The fence allows relative free lateral diffusion of lipids within compartments but restricts movement between compartments.…”

Section: Box 3 Extrapolating From Model Membranes To the Plasma Membranementioning

confidence: 99%

Lipid rafts: contentious only from simplistic standpoints

Hancock

2006

Nat Rev Mol Cell Biol

751

716

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The hypothesis that lipid rafts exist in plasma membranes and have crucial biological functions remains controversial. The lateral heterogeneity of proteins in the plasma membrane is undisputed, but the contribution of cholesterol-dependent lipid assemblies to this complex, non-random organization promotes vigorous debate. In the light of recent studies with model membranes, computational modelling and innovative cell biology, I propose an updated model of lipid rafts that readily accommodates diverse views on plasma-membrane micro-organization.A widely accepted hypothesis in contemporary cell biology is that freely diffusing, stable, lateral assemblies of sphingolipids and cholesterol, which are termed lipid rafts 1-3 , constitute an important organizing principle for the plasma membrane. The basic concept is that lipid rafts can facilitate selective protein-protein interactions by selectively excluding or including proteins. This lipid-based sorting mechanism has been widely implicated in the assembly of transient signalling platforms and more permanent structures such as the immunological synapse, as well as in the sorting of proteins for entry into specific exocytic and endocytic trafficking pathways [1][2][3] . Despite the undoubted theoretical utility of lipid rafts to many cell biological processes, the basic hypothesis that stable lipid rafts exist at all in biological membranes is under intense scrutiny 4,5 . This is partly because lipid rafts, if they exist in resting cell membranes, are too small to be resolved by fluorescent microscopy and have no defined ultrastructure; therefore, proving their existence is problematic. This article will consider the biophysical properties of model membranes that underpin the lipid raft hypothesis, and the limitations of the biochemical approaches that have been used to study rafts in biological membranes that largely account for the current debate on the hypothesis mentioned above. After examining the challenges that are involved in correlating observations, which have been made in model and cellular membranes, I focus on synthesizing recent data on the size of lipid domains in model membranes with observations that have been obtained by imaging intact plasma membranes. These imaging approaches include single particle tracking (SPT), single fluorophore video tracking (SFVT), fluorescence resonance energy transfer (FRET), homo-FRET and electron microscopy (EM). On the one hand, these studies challenge the simplistic null hypothesis that lipid-based assemblies, such as lipid rafts, do not exist in biological membranes. On the other hand, it is timely to reconsider the raft hypothesis in the light of these new data because the consensus model that emerges is more complex than a simplistic notion of stable, freely diffusing lipid rafts. Some intriguing new questions aboutCompeting interests statement The author declares no competing financial interests. DATABASES

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Phospholipids undergo hop diffusion in compartmentalized cell membrane

Cited by 877 publications

References 40 publications

Lipid Lateral Mobility in Cochlear Outer Hair Cells: Regional Differences and Regulation by Cholesterol

Lipid Lateral Mobility in Cochlear Outer Hair Cells: Regional Differences and Regulation by Cholesterol

The human serotonin1A receptor exhibits G-protein-dependent cell surface dynamics

Lipid rafts: contentious only from simplistic standpoints

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