Caveolin-1 (cav-1) is an important player in cell signaling and endocytosis that has been shown to colocalize with cholesterol-rich membrane domains. Experimental studies with varying cav-1 constructs have suggested that it can induce both cholesterol clustering and membrane curvature. Here, we probe the molecular origin of membrane curvature and cholesterol clustering by cav-1 by using coarse-grain molecular dynamics simulations. We have performed a series of simulations of a functionally important cav-1 construct, comprising the membrane-interacting domains and a C-terminal palmitoyl tail. Our results suggest that cav-1 is able to induce cholesterol clustering in the membrane leaflet to which it is bound as well as the opposing leaflet. A positive membrane curvature is observed upon cav-1 binding in cholesterol-containing bilayers. Interestingly, we observe an interplay between cholesterol clustering and membrane curvature such that cav-1 is able to induce higher membrane curvature in cholesterol-rich membranes. The role of the cav-1 palmitoyl tail is less clear and appears to increase the membrane contacts. Further, we address the importance of the secondary structure of cav-1 domains and show that it could play an important role in membrane curvature and cholesterol clustering. Our work is an important step toward a molecular picture of caveolae and vesicular endocytosis.
caveolin-1 (cav-1) protein is an integral component of caveolae and
has been reported to colocalize with cholesterol and sphingomyelin-rich
curved membrane domains. Here, we analyze the molecular interactions
between cav-1 and sphingomyelin containing bilayers using a series
of coarse-grain simulations, focusing on lipid clustering and membrane
curvature. We considered a palmitoylated-cav-1 construct interacting
with phospholipid/cholesterol membranes with asymmetrically distributed
sphingomyelin, varying between 5 and 15% in total. We observe that
cav-1 binds to the intracellular leaflet and induces a small positive
curvature in the leaflet to which it is bound and an opposing negative
curvature in the extracellular leaflet. Both cholesterol and sphingomyelin
are observed to cluster in cav-1 bound membranes, mainly in the extracellular
leaflet. Due to their negative spontaneous curvature, clustering of
cholesterol and sphingomyelin facilitates membrane curvature such
that the extent of either cholesterol or sphingomyelin clustering
is dependent on the curvature induced. Our results suggest that cav-1
binding induces concentration-dependent curvature effects in sphingomyelin-rich
membranes. Overall, our work is an important step in understanding
the molecular basis of curvature and lipid clustering in cav-1 bound
Caveolin-1 (cav-1) is a multi-domain membrane protein that is a key player in cell signaling, endocytosis and mechanoprotection. It is the principle component of cholesterol-rich caveolar domains and has been...
Chronic inflammation in the middle ear may result in functional impairment of the chorda tympani nerve, which carries taste from the anterior two-thirds of the tongue. This may lead to impaired taste sensation. Timely intervention and adequate disease clearance may help the chorda tympani nerve to recover. Gustatory function of 107 patients who underwent Tympanoplasty for Chronic otitis media (mucosal type) was evaluated in a cohort of Indian patients. To compare the preoperative and postoperative gustatory function in these patients taste scores were documented preoperatively, and at 6 weeks and 3 months postoperatively, in an effort to document taste function improvement after disease clearance. The taste scores thus obtained were recorded and analyzed. A significant improvement in taste threshold postoperatively in comparison to the preoperative taste scores (p = 0.001) was found. It was observed that age of the patient and duration of illness have a significant impact on the recovery of taste function. Our study suggests that taste perception improves over a period of time after successful tympanoplasty in patients with chronic otitis media (mucosal type).
Cell signaling networks are generally initiated at the cell membrane and mediated by receptors such as the G proteincoupled receptors (GPCRs). Adjacent to the cell membrane lies a complex network of proteins-the actin cytoskeleton to which several structural and physiological roles have been attributed. An emerging role of the cytoskeleton is to modulate GPCR function and organization, either directly or indirectly. The GPCR-cytoskeleton cross-talk is a complex hierarchical process where each step has its own set of rules and combinations. Due to the inherent complexity involved at each step and the multiple spatio-temporal levels, a complete picture is yet to emerge. In this review article, we provide an overview of actin-membrane interactions and how they modulate GPCR function and organization. In this context, we briefly discuss the structural characterization of actin monomers and filaments together with their interactions with partner proteins, such as the actin binding proteins. The effect of actin interactions on membrane domains is examined that assumes significance in light of membrane modulated effects in GPCR function. We aim to bring together concepts in GPCR signaling and cytoskeletal dynamics towards addressing emerging concepts in GPCR function.
Objective: The objective of this study was to demonstrate and evaluate the suspending property of newly isolated, purified, and characterized Hygrophila spinosa seed mucilage in liquid oral suspensions of paracetamol.Methods: Isolation of mucilage from H. spinosa seeds was done by maceration process, and then it was characterized by phytochemical screening, solubility, pH, swelling index, flow rate, viscosity, loss on drying, and cytotoxicity. The characterized mucilage was then used as a suspending agent for the preparation of suspensions containing paracetamol as a model drug. The prepared formulations were then evaluated for different parameters such as sedimentation volume, redispersibility, flow rate, pH, viscosity, and other physical examination.Results: The isolated mucilage is a polysaccharide with no impurities and nontoxic in nature. It has got enough swellability and good viscosity. The prepared suspensions were evaluated, and the results such as sedimentation volume, redispersibility, flow rate, pH, viscosity, and other physical examination showed its suspending property.Conclusion: The study revealed that a lesser amount of H. spinosa seed mucilage can produce a good suspension. By this study, it could be find out that a 1/5th quantity of mucilage (0.2%) is only required to prepare a suspension of paracetamol when compared with suspensions prepared of compound tragacanth (1%) and sodium carboxymethyl cellulose (1%) as suspending agents. Thus, by this study, it can be stated that the mucilage from H. spinosa possesses all the criteria needed by a standard suspending agent.
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