Mobility of cell surface receptors: a re‐evaluation

Cherry, Richard J.; Smith, Patricia R.; Morrison, Ian; Fernández, Nelson

doi:10.1016/s0014-5793(98)00595-x

Cited by 38 publications

(35 citation statements)

References 34 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These methodologies supported by digital image processing add valuable information to the dynamic data about the spatial distribution and compartmentation of membrane constituents. In general, these approaches provide evidence for the domain-like distribution of lipids and proteins in biological membranes (17,30,31).…”

Section: Advanced Cell Biophysical and Molecular Biological Methodolomentioning

confidence: 99%

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Vereb

Szöllősi

Matkó

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

472

385

View full text Add to dashboard Cite

The fluid mosaic membrane model proved to be a very useful hypothesis in explaining many, but certainly not all, phenomena taking place in biological membranes. New experimental data show that the compartmentalization of membrane components can be as important for effective signal transduction as is the fluidity of the membrane. In this work, we pay tribute to the Singer-Nicolson model, which is near its 30th anniversary, honoring its basic features, ''mosaicism'' and ''diffusion,'' which predict the interspersion of proteins and lipids and their ability to undergo dynamic rearrangement via Brownian motion. At the same time, modifications based on quantitative data are proposed, highlighting the often genetically predestined, yet flexible, multilevel structure implementing a vast complexity of cellular functions. This new ''dynamically structured mosaic model'' bears the following characteristics: emphasis is shifted from fluidity to mosaicism, which, in our interpretation, means nonrandom codistribution patterns of specific kinds of membrane proteins forming smallscale clusters at the molecular level and large-scale clusters (groups of clusters, islands) at the submicrometer level. The cohesive forces, which maintain these assemblies as principal elements of the membranes, originate from within a microdomain structure, where lipid-lipid, protein-protein, and protein-lipid interactions, as well as sub-and supramembrane (cytoskeletal, extracellular matrix, other cell) effectors, many of them genetically predestined, play equally important roles. The concept of fluidity in the original model now is interpreted as permissiveness of the architecture to continuous, dynamic restructuring of the molecular-and higherlevel clusters according to the needs of the cell and as evoked by the environment.

show abstract

Section: Advanced Cell Biophysical and Molecular Biological Methodolomentioning

confidence: 99%

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Vereb

Szöllősi

Matkó

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

472

385

View full text Add to dashboard Cite

show abstract

“…In order to have a more integrative understanding of cell biology, major efforts have been accomplished to describe motions of living objects, from the cellular to the molecular scale, with improved resolution. To this end, a large set of single-particle-tracking (SPT) techniques has been actively developed in the past 10 years, based on sparsely labeling individual proteins, or individual vesicles (Zhang et al, 1993;Cherry et al, 1994;Kusumi and Sako, 1996;Cherry et al, 1998;Craig and Lichtman, 2001) with beads (Geerts et al, 1987;Cognet et al, 2003), fluorescent antibodies, autofluorescent fusion proteins (Tsien, 1998) or quantum dots (Dahan et al, 2003). For technical reasons, single molecule methods have been mostly successful to study transmembrane proteins (Craig and Lichtman, 2001;Borgdorff and Choquet, 2002;Daumas et al, 2003), and mechano-enzymes in cell-free systems (Block, 1998;Spudich, 2001).…”

Section: Introductionmentioning

confidence: 99%

Statistical Analysis of Sets of Random Walks: How to Resolve Their Generating Mechanism

2007

View full text Add to dashboard Cite

The analysis of experimental random walks aims at identifying the process(es) that generate(s) them. It is in general a difficult task, because statistical dispersion within an experimental set of random walks is a complex combination of the stochastic nature of the generating process, and the possibility to have more than one simple process. In this paper, we study by numerical simulations how the statistical distribution of various geometric descriptors such as the second, third and fourth order moments of two-dimensional random walks depends on the stochastic process that generates that set. From these observations, we derive a method to classify complex sets of random walks, and resolve the generating process(es) by the systematic comparison of experimental moment distributions with those numerically obtained for candidate processes. In particular, various processes such as Brownian diffusion combined with convection, noise, confinement, anisotropy, or intermittency, can be resolved by using high order moment distributions. In addition, finite-size effects are observed that are useful for treating short random walks. As an illustration, we describe how the present method can be used to study the motile behavior of epithelial microvilli. The present work should be of interest in biology for all possible types of single particle tracking experiments.

show abstract

“…However, other than the inclusion of the benzodiazepine sensitivity-conferring ␥ subunit, the molecular composition of the receptors measured in these mobility studies was not known. In this work, we have expressed recombinant subunits in COS7, HEK293, and PC12 cells and used immunocytochemistry, fluorescence photobleach recovery (FPR) [Elson et al, 1976;Watson et al, 1999], and single particle tracking (SPT) [Cherry et al, 1998;Brown et al, 2000] to gain insight into the role that individual subunits play and mechanisms by which receptors are clustered and immobilised. Immunocytochemistry of fixed and permeabilised ␣1 GABA A R subunit cDNA transfected COS7 and HEK293 cells shows that the ␣1 subunit peptide is retained in an intracellular compartment that has the morphological characteristics of the endoplasmic reticulum (ER) (Figs.…”

Section: Introductionmentioning

confidence: 99%

Lateral mobility and anchoring of recombinant GABA_A receptors depend on subunit composition

Perán

Hicks

Peterson

et al. 2001

Cell Motil. Cytoskeleton

View full text Add to dashboard Cite

The clustering of type A gamma-aminobutyric acid receptors (GABA(A)R) at discrete and functionally significant domains on the nerve cell surface is an important determinant in the integration of synaptic inputs. To discern the role that the subunits of the GABA(A)R play in determining the receptor's cell surface topography and mobility, the alpha1, beta1, beta3, and gamma2s subunits were transfected into COS7, HEK293, and PC12 cells and the distribution and cell surface mobility of these recombinant receptors were examined. Our results show that alpha1 subunits are retained in the endoplasmic reticulum while beta1 and beta3 subunits are sorted to the plasma membrane where they form clusters. Co-expression and co-assembly of alpha1 and beta3 subunits result in the rescue of intracellular alpha1 subunits, which are transported as alphabeta subunit complexes to the cell surface where they formed clusters. Fluorescence photobleach recovery and single particle tracking of recombinant receptors show that, despite clustering, beta3 subunit homooligomers are mobile within a cell surface domain. Inclusion of alpha1 in beta3 or beta3gamma2s complexes, however, dramatically reduces the receptor's lateral mobility in COS 7 and PC12 cells and anchors GABA(A)Rs on the cell surface, suggesting the formation of a direct link to a component of the cytoskeleton. The mobility of recombinant receptors that include the alpha1 subunit mirrors the mobility of GABA(A)Rs on cell bodies and dendrites of cortical and spinal cord neurons. The results suggest that incorporation of alpha1 subunits give rise to a population of GABA(A)Rs that are immobilized on the cell surface.

show abstract

Mobility of cell surface receptors: a re‐evaluation

Cited by 38 publications

References 34 publications

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Statistical Analysis of Sets of Random Walks: How to Resolve Their Generating Mechanism

Lateral mobility and anchoring of recombinant GABA_A receptors depend on subunit composition

Contact Info

Product

Resources

About

Mobility of cell surface receptors: a re‐evaluation

Cited by 38 publications

References 34 publications

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Statistical Analysis of Sets of Random Walks: How to Resolve Their Generating Mechanism

Lateral mobility and anchoring of recombinant GABAA receptors depend on subunit composition

Contact Info

Product

Resources

About

Lateral mobility and anchoring of recombinant GABA_A receptors depend on subunit composition