https://www.normalesup.org/~vorgogoz/articles/D.pachea-references/alternative-splicing/Stamm2005-alternative-splicing-review.pdf

Function of alternative splicing.

A fundamental property of many plasma-membrane proteins is their association with the underlying cytoskeleton to determine cell shape, and to participate in adhesion, motility and other plasma-membrane processes, including endocytosis and exocytosis. The ezrin–radixin–moesin (ERM) proteins are crucial components that provide a regulated linkage between membrane proteins and the cortical cytoskeleton, and also participate in signal-transduction pathways. The closely related tumour suppressor merlin shares many properties with ERM proteins, yet also provides a distinct and essential function.

http://loyce2008.free.fr/MENINGO/Ezrine%20et%20actin/Bretscher,%20erm%20proteins%20integrators%20at%20the%20cell%20cortex,%20Nat%20REv%20CEll%20Biol%202002.pdf

ERM proteins and merlin: integrators at the cell cortex

Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

The spectrin-based membrane skeleton of the humble mammalian erythrocyte has provided biologists with a set of interacting proteins with diverse roles in organization and survival of cells in metazoan organisms. This review deals with the molecular physiology of spectrin, ankyrin, which links spectrin to the anion exchanger, and two spectrin-associated proteins that promote spectrin interactions with actin: adducin and protein 4.1. The lack of essential functions for these proteins in generic cells grown in culture and the absence of their genes in the yeast genome have, until recently, limited advances in understanding their roles outside of erythrocytes. However, completion of the genomes of simple metazoans and application of homologous recombination in mice now are providing the first glimpses of the full scope of physiological roles for spectrin, ankyrin, and their associated proteins. These functions now include targeting of ion channels and cell adhesion molecules to specialized compartments within the plasma membrane and endoplasmic reticulum of striated muscle and the nervous system, mechanical stabilization at the tissue level based on transcellular protein assemblies, participation in epithelial morphogenesis, and orientation of mitotic spindles in asymmetric cell divisions. These studies, in addition to stretching the erythrocyte paradigm beyond recognition, also are revealing novel cellular pathways essential for metazoan life. Examples are ankyrin-dependent targeting of proteins to excitable membrane domains in the plasma membrane and the Ca(2+) homeostasis compartment of the endoplasmic reticulum. Exciting questions for the future relate to the molecular basis for these pathways and their roles in a clinical context, either as the basis for disease or more positively as therapeutic targets.

Spectrin and Ankyrin-Based Pathways: Metazoan Inventions for Integrating Cells Into Tissues

Structural Basis of Integrin Activation by Talin

The FERM domain: A unique module involved in the linkage of cytoplasmic proteins to the membrane

Schwannomin isoform-1 interacts with syntenin via PDZ domains.

Specific loss of protein kinase activities in senescent erythrocytes

Purification de la proteine codee par le gene suppresseur de tumeur NF2 a partir d'erythrocytes humains. Contexte: La neurofibromatose de type 2 (NF2) est une maladie dominante autosomique qui predispose au developpement de tumeurs au niveau des nerfs crâniens et des nerfs spinaux. La proteine codee par le gene suppresseur de tumeurs NF2, connue sous le nom de Merlin/Schwannomin, fait partie de la superfamille des proteines 4,1 impliquees dans l'interface entre le cytosquelette et la membrane plasmatique. Methodes: Lors de l'extraction selective des proteines associees a la membrane cellulaire d'erythrocytes plasmatiques (fantomes d'hematies) au moyen d'une solution dont la force ionique est faible, la majeure partie de la proteine NF2 demeure associee aux vesicules inversees depourvues de spectrine-actine. L'analyse par buvardage Western a demontre la presence d'un polypeptide de ∼70 kDa dans la membrane plasmatique erythrocytaire. L'elimination quantitative de la proteine NF2 des vesicules inversees a ete effectuee au moyen d'iodure de potassium 1,0 M, un traitement qui extrait les proteines membranaires peripheriques fortement liees. Resultats: Ces resultats sont compatibles avec un nouveau mode d'association de la proteine NF2 a la membrane erythrocytaire qui est distinct des interactions membranaires connues au sujet des proteines 4,1. Plusieurs strategies de purification fondees sur ces proprietes biochimiques ont ete elaborees pour isoler la proteine NF2 native des fantomes d'hematies humaines. Nous avons quantifie approximativement ∼41-65 000 molecules de proteine NF2 par erythrocyte en utilisant la proteine NF2 purifiee et la proteine NF2 recombinante comme standards internes. Conclusion: Ces donnees sont compatibles avec la presence de la proteine NF2 dans la membrane des erythrocytes humains. L'identification de la proteine NF2 dans la membrane des erythrocytes humains permettra de decouvrir de nouveaux modes d'interactions de la proteine NF2 dans les cellules de mammiferes au moyen de techniques puissantes de biochimie et de genetique erythrocytaire.

/pdf/purification-of-the-nf2-tumor-suppressor-protein-from-human-3cgf2rrf3x.pdf

Hitesh K. Jindal

Papers

The FERM domain: A unique module involved in the linkage of cytoplasmic proteins to the membrane

Schwannomin isoform-1 interacts with syntenin via PDZ domains.

Specific loss of protein kinase activities in senescent erythrocytes

Purification of the NF2 Tumor Suppressor Protein from Human Erythrocytes