Annexin A2 Mediates Dysferlin Accumulation and Muscle Cell Membrane Repair.

Muscle cell plasma membrane is frequently damaged by mechanical activity, and its repair requires the membrane protein dysferlin. We previously identified that, similar to dysferlin deficit, lack of annexin A2 (AnxA2) also impairs repair of skeletal myofibers. Here, we have studied the mechanism of AnxA2-mediated muscle cell membrane repair in cultured muscle cells.

Mitochondrial redox signaling enables repair of injured skeletal muscle cells.

Strain and physical trauma to mechanically active cells, such as skeletal muscle myofibers, injures their plasma membranes, and mitochondrial function is required for their repair. We found that mitochondrial function was also needed for plasma membrane repair in myoblasts as well as nonmuscle cells, which depended on mitochondrial uptake of calcium through the mitochondrial calcium uniporter (MCU). Calcium uptake transiently increased the mitochondrial production of reactive oxygen species (ROS), which locally activated the guanosine triphosphatase (GTPase) RhoA, triggering F-actin accumulation at the site of injury and facilitating membrane repair.

Mechanism of Ca²⁺-triggered ESCRT assembly and regulation of cell membrane repair.

In muscle and other mechanically active tissue, cell membranes are constantly injured, and their repair depends on the injury-induced increase in cytosolic calcium. Here, we show that injury-triggered Ca(2+) increase results in assembly of ESCRT III and accessory proteins at the site of repair. This process is initiated by the calcium-binding protein-apoptosis-linked gene (ALG)-2.

S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells.

Cell migration and invasion require increased plasma membrane dynamics and ability to navigate through dense stroma, thereby exposing plasma membrane to tremendous physical stress. Yet, it is largely unknown how metastatic cancer cells acquire an ability to cope with such stress. Here we show that S100A11, a calcium-binding protein upregulated in a variety of metastatic cancers, is essential for efficient plasma membrane repair and survival of highly motile cancer cells.

Prominin-2 expression increases protrusions, decreases caveolae and inhibits Cdc42 dependent fluid phase endocytosis.

Background: Membrane protrusions play important roles in biological processes such as cell adhesion, wound healing, migration, and sensing of the external environment. Cell protrusions are a subtype of membrane microdomains composed of cholesterol and sphingolipids, and can be disrupted by cholesterol depletion. Prominins are pentaspan membrane proteins that bind cholesterol and localize to plasma membrane (PM) protrusions.

Ceramide transfer protein and cancer.

Sphingolipids are important structural components of membranes, and play an equally important role in basic cellular processes as second messengers. Recently, sphingolipids are receiving increasing attention in cancer research. Ceramide is the central molecule that regulates sphingolipid metabolism forming the basic structural backbone of sphingolipids and the precursor of all complex sphingolipids.

Two and three-dimensional pattern recognition of organized surfaces by specific antibodies.

Understanding molecular recognition of supramolecules for solid substrates is essential for designing chemical sensors and molecular devices. The rules of molecular recognition are well established at the level of single molecules. However, during the transition from molecular-scale devices to macroscopic devices, issues concerning control over recognition that are well-established at the molecular level become much more complex.

Antibody labeling of cholesterol/ceramide ordered domains in cell membranes.

A monoclonal antibody raised against mixed monolayers of 60:40 mol % cholesterol/C16-ceramide of known structure was used to label cholesterol/ceramide-rich domains in cell membranes. The antibody, Cer-Chol 405F specifically recognizes the mixed crystalline and homogeneous phase in monolayers, but it does not interact with either of the components separately. It interacts differently with mixed monolayers that contain ceramides of different acyl chain length.

Structure of cholesterol/ceramide monolayer mixtures: implications to the molecular organization of lipid rafts.

The structure of monolayers of cholesterol/ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two components within a range of compositions of cholesterol/ceramide between 100:0 and 67:33. The mixed phase coexists with the ceramide crystalline phase in the range of compositions between 50:50 and 30:70; between 30:70 and 0:100 only the highly crystalline phase of ceramide was detected.